 I'd like to welcome you all to this third in the series of winter lectures from the 50th celebration of the Faculty of Medicine, Health Sciences. My name's Mike Finlay, I'm the Professor of Oncology. And on behalf of John Luth, the CEO of the Cancer Society Auckland in Northland, I'd like to welcome you to this evening's lectures. I'm sure you'll find them most entertaining and informing. We have a couple of housekeeping rules. One is I've left my mobile phone out to remind me to remind you to switch your mobile phone onto silent, so you can see I've done mine. The second is that if there's an emergency, there are exits to use. If one needs the bathroom, the bathrooms are outside the lecture theatre. And so with that done, I'd like to firstly introduce the director, Sue Brewster, executive director of the Auckland Medical Research Foundation, along with the Cancer Society of Auckland and Northland and the Medical Health Sciences, the co-sponsors of this session. So, Sue, would you like to come forward? Thank you very much. And what a fantastic turnout there is here tonight. Even on a rainy night, we couldn't put anyone off. And it's just wonderful to see you all here. Thank you very much. It's a real pleasure to be partnering with the Faculty of Medical and Health Sciences and the Cancer Society for this particular lecture and in celebration of the 50th anniversary. So look, I don't think there's, I'm just going to do the buttons, I don't think there's too much that I can actually say about funding research into cancer treatments because I think this young lady, Kiriana's story, will really say it all. So in March 2015, Kiriana Elliott woke up with a bit of a sore ankle, feeling a bit tired, not a usual buzzy self. And then one month later, she was diagnosed with leukemia. Kiriana's mum, Ursula, described that day as the worst day in their family's lives. But the good news is that prior to Kiriana's diagnosis, Dr. Andrew Wood, a pediatrician specializing in child blood cancers, was awarded our AMRF, Douglas Goodfellow Repatriation Fellowship. And we brought him back from Philadelphia, where he was working. This funding allowed Dr. Wood to return home and advance his research into childhood leukemia. And he also was Kiriana's specialist, caring for her during her cancer care and her treatments. So then we fast forward to May 2017, and Kiriana's treatments had all finished and she was allowed to return home to her family. Tonight, I'm so delighted to say that Kiriana is in full remission. She's back to playing hockey and netball and doing dancing that she absolutely loves. And of course, Kiriana and her family are so grateful to Dr. Wood and his team for the extraordinary care that they received during that journey. But I think the big thing they also acknowledge is that without funding into research for the cancer treatments, Kiriana's outcomes could have been very, very different. So I'd like to finish by thanking our incredible presenters who are here tonight and presenting on behalf of our research community who are all working to provide advancement in medicine and health. But most of all, I'd like to thank our supporters who are here tonight because without your support, a bright and healthy future for children like Kiriana just wouldn't be possible. So look, thank you very much. Thank you everyone for coming. And please, you've got feedback, backforms like these in your folders or you can receive them on the way out in the door. Please do take two minutes to fill them out. They're really important so we can keep providing these lectures for you. Thank you very much and enjoy. Kia ora tātou, good evening everyone. It's my great pleasure to introduce a man who, I'm sure to many of you, doesn't actually need much of an introduction. It's distinguished Professor Bill Denney. And Bill has had a stellar career in New Zealand and overseas in terms of cancer research. Originally trained here at Auckland University and then Oxford University. Bill has had a string of achievements and we'd be here for the next hour if I was to read them all out. But I think the most, perhaps the one's recognition that I really want to make is he's a Rutherford Medalist of the Royal Society of New Zealand and Adrian Albert Medalist of the UK Royal Society and an Officer of the New Zealand Order of Merit for his services to cancer research. Bill is the current Director of the Auckland Cancer Society Research Centre. Please welcome Bill Denney. Thank you very much, John. And welcome everyone here. It's really good to see so many people here on, as they say, a wet night. What I'd like to do is to talk briefly about the work we're doing in the Cancer Centre to develop new drugs for cancer therapy. Now drug development is a very multidisciplinary exercise. You need, first of all, the computer modelers to try to design the targets you want to hit. You need the chemists, obviously, to design and make the drugs that you want those targets to hit with. You need the biologists, the pharmacologists, the cancer clinicians to take those drugs further into their development. And the work in the lab is enabled by collaborations outside with other scientists and clinicians and with outside companies as well because it's a very expensive journey outside the lab as well to get a drug through into clinical trial. And we've done this with a number of large commercial companies, with a number of small companies, and even there on the bottom here, some of our own venture capital startup companies. And with these partners, the Centre is to date taking 12 new cancer drugs into clinical trials, some in New Zealand and the rest around the world. Now the early drugs we used for cancer targeted DNA. And that was logical because it's errors in the DNA that cause the errors in the proteins which cause cells to become cancerous. But unfortunately, at that time, we didn't know enough to be able to target the subtle differences in the sequence of DNA that really the mutations have all about. And instead, these drugs, likely intercalators, just broke the DNA strands. And the drugs, like the alkylaters, linked the two strands together. And both of those things means the cell can't abide, the cell dies, and these drugs are very effective at killing cancer cells. They're relatively unselective at killing normal cells as well, so they have toxicities associated with them. But what we understand today is the staggering complexity of a human cell and the proteins inside it. Each of you is made up of about 10 trillion cells, so they're all very small. But even so, each cell packs into it more than 10,000 different proteins. And a lot of these proteins are linked and hooked up into signalling networks here which exchange signals among each other and signals from the outside that control when a cell divides and when it doesn't. A lot of them act essentially as switches to turn things on and off. And each of those individual proteins are made up of thousands of different atoms so that each protein has a very specific structure. And it's only when we can get down into the atomic level and look at these at the level of each atom that we see the unique differences between them and can start designing compounds that target one protein among the 10,000 or so. So what I'd like to do today is to talk very briefly about three types of projects in the center. One of them is drugs to control these signalling enzymes. And you can see here a small part of this particular EGF receptor enzyme. And each of these little green bumps is a single atom. So you can see now that at that level we can see this big gap, this big hole in the protein and we can learn how to design drugs to bind into that hole. I'd also talk briefly about two other projects. One, a long-standing project, is drugs targeting the hypoxic cells that are specific to cancers because they exist a long way from the bloodstream and they lack oxygen. And finally, a little bit about the way we're now finally starting to approach the even more complex immune system to talk about drugs which can boost the immune system's capability. But coming back to the first point, the EGF receptor is one of these switch proteins. It happens to sit in the membrane, across the membrane, and it takes signals from outside, transmits them through into the inside and essentially acts as a switch to tell cells whether to turn on or turn off. And of course some of the problems is that mutations cause these enzymes to be stuck in the old position where they're continually dividing. Now you can see here that by use of these modeling techniques we can, in fact, design drugs that fit very tightly and very neatly into this pocket that's been provided in the enzyme and shut it off from functioning. The trouble with this is that these drugs bind reversibly, they come in, they bind, they leave again and the enzyme is only blockaded when there's high amounts of drug in the system. But as that drug gets metabolized, the drugs can move out again and the period of shutdown is relatively smaller than we would like. So our particular contribution to this area has been to note that these drugs bind in this pocket in the same way each time and therefore we can use that general binding to deliver a fairly reactive unit on the drug to a reactive unit on the protein. And separately those two things are not very reactive but bring them close together and they link to form a permanent bond. So those drugs are then irreversibly bound and the enzyme is shut down permanently. And connectively from our collaboration with Pfizer was the first of these irreversible inhibitors to reach human trials a few years back. And we've used on it a particular locking unit called an acrylamide. And to date there are about 10 of these irreversible inhibitors in clinical use, targeting different enzymes and therefore being of different structure and generated to many different companies but all of them use the original locking unit that we originally devised. The second area I'd like to talk about briefly is to selectively targeting the so-called hypoxic or low oxygen cells that exist in the center of solitumas. This is a cross-section through a solitumat and you can see here the blood vessels. Here you can see in the red and black the oxygenated cells close to the blood vessels still fully dividing and far away from the blood vessels in the green you see the hypoxic cells that are viable but shut down and not cycling. And these are really unique to cancer tissue. So there's a difference, can we exploit that difference? Because these hypoxic cells are difficult to kill with conventional drugs because they're remote from the blood vessels, they're shut down, they're not replicating so most of the standard drugs don't work. But if you do treat these tumors with normal drugs and you kill out all the oxygenated cells then oxygen is free to flow again and turn these cells back on to regenerate the tumor and that's what happens in so many cases. So we've been looking at what we call hypoxia-activated pro-drugs which contain an oxygen sensor linked through to an active form of a drug and these are designed to be fairly stable, safe and non-toxic until they distribute through into these hypoxic regions when the sensor recognises the lack of oxygen and then starts a process that results in fragmentation of the drug to release the active form. And ideally then this active form will redistribute to kill some of the oxygenated cancer cells as well. We currently have three drugs that have reached clinical trial in this area, PO-104, Tulloxotanib and a drug called CPT-006. And you can see from this example of Tulloxotanib treating an animal model of a solid tumor before treatment you can image the hypoxic cells in green but after treatment with the drug those have all gone away, they've all been taken out. So these drugs do work in these models and we're hopeful that we'll get successful clinical trials with one of these compounds in the near future. And finally, the immune system until recently was so complicated that we couldn't even contemplate how we could affect that, how we could help that to its job is to seek out and destroy foreign cells. So it's our frontline defence against cancers but cancers have many ways in which they can first of all block the processes by which the immune cells take out cancers and secondly simply weaken the immune response generally. And the project in the centre here targeted at the second point is looking at another protein called CSF1 receptor which is secreted by cancers and in so doing it can recruit the patient's own immune cells or macrophages to start generating growth factors which cause the cells to be stimulated and to grow. So the effect it subverts the immune system's response and by shutting this down we can stop this process. And so we've been again in the early stage, there's so far only two drugs in the clinic targeting this enzyme. It's early days but we have a programme running for the last couple of years looking at modelling the pockets in this enzyme where we can bind drugs to and now have a series of selective and very potent compounds that we're trying to evolve through into finding a clinical candidate in the next couple of years. But the question that we can pose is what's the value of all this research? What sort of impact is it making in cancer treatment when you get out of the lab? And one of the best ways we could perhaps talk about that with a single number is looking at the percentage of patients in New Zealand who survive for 10 years or longer after diagnosis. And you can see that through a combination of better lifestyles, better screening, because early screening is important and better treatment and that includes better surgery, radiotherapy and not least the whole pile of new drugs that have been coming through over the last many years. The 10 year plus year survival rate has improved from less than a quarter of all people until when I started work actually, through to about nearly 60% now. And that's a real improvement. But of course it begs the immediate question, how can we make that better? How can we continue this improvement? And I think just to finish off, there are three areas which I think are going to bear on that in the near future. First of all, earlier and more accurate screening because if we can identify cancers early, we can treat them more effectively. And being able to identify the tiny amounts of tumor DNA that's released by dying tumor cells into the bloodstream at an early stage will allow us to have, simply detect that DNA through blood tests. And that will obviously be very much cheaper, very much more simpler than what we have to go through now. Now this technology is not quite there yet and there's an awful lot of work going on around the world and I'm fairly confident that in the next few years we'll be seeing increasingly our ability to identify tumor DNA from blood samples early on. Secondly, better matching of patients and drugs. The way in which a patient responds to a drug depends on the genetics of that tumor and the genetics of the patient. And in any particular tumor treating a group of people with the same type of cancer, you'll get some people that are not, that whether the drug is not effective and we really don't want to be treating those people with that drug. So based on tumor and patient genetics, better matching of patients to drugs in a personalized approach is coming along very rapidly and I think we'll hear a bit more about that later on. And finally, there is a whole slew of new drugs coming through and particularly the immunotherapy drugs. And these are increasingly based on individual patient genetics. And I think those three areas where we are seeing big progress going on in the science will feed through to treatment in the next few years. So I've very briefly, I'm afraid, discussed a few of the cancer drug development programs going on in the center. And of course, I remind you that across the faculty there's a very large research effort into all areas, all aspects of cancer diagnosis, treatment and therapy and support. And thank you very much for your attention. Thank you very much, Bill, for your run away. We have a format where there's time, and we have time for one question from the audience. Stunned a bit, I've got a question. Bill, what's the biggest challenge for you in your discipline of medicinal chemistry for the next 10 years? Keeping up with the flood of data that's coming through from everybody else, basically, so that you can actually do something that's different to what everyone else is doing. With the kinase inhibitors I talked about, we were the first to do a certain thing that's followed through with everyone else. The hypoxia programs we've been running for a long time, none of those are yet successful, but we finally know, I think, all of the things we need to know. And the next compound, a couple of compounds that come through from the lab have a much better chance of actually getting approved. Well done, thank you very much, Bill. It's exciting work. I'd like to move on and introduce our next speaker, who's Professor Leiming Cheng, who is at the Auckland Cancer Society Research Centre as well. She's been well-trained here but moved overseas to Toronto and Seattle, and worked there before coming there to get up, the stromal targeting group at the centre, specialising in approaches to restore the capacity of the normal cells in the tumour stroma to fight cancer. The type of the talk is boosting our immune system to fight cancer. Leiming. Thank you. And thank you everyone for coming. Yes, so I work at the Auckland Cancer Society Research Centre, which is just over there next to the toilets, and you're welcome to come visit us. Now, what I want to do in my talk is to expand upon some of the advances and approaches that harness the immune system to kill the cancer. Now, we all, everybody here, has a functioning immune system that we use to ward off infections from bugs and bacterium and viruses, as well as mutated cancer cells. And by far the most effective way of the immune system that can seek out and destroy the cancer cells are what we call the killer T cells. Now, below, before and after shot of a melanoma cells that have been killed by these white cells, which are the immune T cells. Now, when the immune T cells spots a melanoma cell, it rolls towards it, sniffs around, and when they decide that, yes, indeed, that's a nasty cell that we wish to get rid of, they release a product, a protein called perforin onto the surface, and that serves to punch these Gregbic holes that you might be able to pick out here. And then the cancer cell just releases all its bloods and guts and dies. And then the T cells just go off and find other cancer cells to kill. So they're serial killers. And we've known about these killer T cells since the 1960s, and since the 1990s, we've been madly trying to harness them for use as therapy. And recently, that with all the new latest technologies in our ability to separate these out from the blood of patients and to be able to grow them outside the body in incubators, in, dare I say, giant plastic bags that we use only once in TOS. But none have been found in the Valley of Wales to see turtles yet. None. And those cells, we were half as well, then put back to the patient in a process called adoptive T cell transfer. And in December 2013, Science, one of our top rated scientific journals, claimed it as the breakthrough of the year. But very soon after that, scientists took these endogenous natural T cells and they added bits and pieces to it to make it better. And those are called chimeric antigen receptor, or CAR T cells. Now if I was to liken these two different types of cells to models of CARs, then these are your Toyota Corollas. Very reliable, very dependable, and will get you to work no trouble. But these CAR T cells are your Mercedes-Benzers. They don't get you to work any faster, but you enjoy the two-hour certain rush hour traffic much more. Now, the results from recent clinical trials of CAR T cells for leukemia have come up with statements such as this. Patients had eight pounds of leukemia that just melted away. Now you can tell that it must have come from an American trial because the rest of the world have moved on to metrics, but they're still in pounds and ounces. Now to put this eight pounds of leukemia into some perspective, eight pounds converts to about 3.6 kilos, and the average weight of a leukemia cell is about 2 nanograms. So if you do the calculations, that converts to 2 million million leukemia cells that have been killed. So if I told you that these normal natural T cells are serial killers, these CAR T cells are your weapons of mass destruction. Now unfortunately Auckland doesn't have a factory for making CAR T cells, but I think it would be needed. We could raise the funding somehow to produce CAR T cells and these weapons of mass destruction in our local war against cancer. Now T cells, be it the souped-up CAR T cells or the normal natural T cells, when they get tired from killing they express breaks on their surface. Now scientists have made antibodies to those breaks which covers up the immune checkpoint block, the immune checkpoints which is a more scientific term for the breaks, and they prevent the cells from being, they block the breaks from being applied, and the poor T cells have to continue to kill on and on and on and keep on going no matter how tired and how much it wants to retire. Now initially these antibodies, the immune checkpoint blockades were made so the scientists could use it as tools to understand how T cells were regulated. But when they were trialled as therapy in its own right, the results were absolutely spectacular. And the T cell has lots of immune checkpoints, but the first ones to be trialled were the anti-CTLA4 antibodies, the pillow-moo map and terminal, I don't know, and the second lot were the anti-PD1 antibodies. They were trialled firstly and against advanced malinoma, patients who have failed all previous therapies and were expected to live only a few more months. But on epi for short, the immune checkpoint blockade therapy was found to induce durable responses and some of the patients has now been over 15 years that they have been alive. And this led to oncologists saying it's not inconceivable that patients may live virtually disease-free for years using approaches that harness the immune system. So let's have a closer look at the data. And this is epi on a group of 4,846 malinoma patients. And you can see that there is a drop-off, but if you're alive after three years on epi, then you're expected that you will survive up to well past 10 years. And so that is wonderful and much, much better than the current chemotherapies where it just drops off within a year. But, and in this group of nearly 5,000 patients, we have saved about 1,000. But there's still the other 4,000 that epi could not save. And so the big question is, and the big challenge is, how do we try and bring that tail further up? There are two approaches currently. One is to use the genetic, the tools of precision medicine and sequence the genome of the patients who have responded well and try and identify why they are better responders. And the other way is to use combination therapy. If one immune checkpoint barcade will give you that many cures, then let's add more and more. And both approaches have provided positive results because we now know that the tumors that respond well, they have a higher mutation burden than the ones which are responding badly. And that's because there's a defect in the gene that corrects for all the mutations. And in combination therapy where you add more and more, give more than one immune checkpoint barcade, yes, you can get, you can push the towel up. This is a fee, and you can get 22%, which are alive long, long term. This is the response from Nevolumab or Nevo for short that will give you 48% of the patients getting durable responses. But the combination of the two is greater than the sum of 48 and 22%, so it's synergistic. Now, so why aren't we doing more and more combinations? Well, these immune checkpoint blockades come with a price. They have a lot of bad toxicities associated with it. With IP, for a 22% long-term survival, it comes with 23% of the patients getting bad adverse effects. Nevo is a better drug. It gives you 48% long-term survivors with only 16.3% of adverse toxicities. The combination, unfortunately, the toxicities seem to be also synergistic. And some of these toxicities are so debilitating, the patients choose to come off it. So can we find combinations where you can get better responses but not the toxicities? Now, maybe. This is a replot of the graphs that I showed you, and it's called a waterfall plot. And this is of Nevo and IP against the melanoma of patients. And you can see not all of them, the tumor shrinks, but the majority does. And here are the ones where all the tumor has gone. And as I said, this combination, you have 55% of your patients suffering from grade 3 and 4 adverse events. Now, if we show the waterfall plot from Nevo, same as that one, plus another drug called Epocadostate, I don't make up these names and I don't know who does. Again, there were metastatic melanoma patients that were not expected to survive for long periods. But here, they were getting very good responses, similar to this, and these have all disappeared. But look at a percentage of toxicities, 11% compared with 55%. So Epocadostate belongs to a new class of drugs that are called IDO1 inhibitors. Would people like to hear more about these? Good, thank goodness for that, because I've spent the last 10 years of my life working on these. IDO1 is an enzyme that converts tryptophan to chyurinine. Tryptophan is an essential amino acid that cells require in order to make proteins. Now, it's been shown that many cancer cells express IDO1, which accelerates conversion of tryptophan to chyurinine, and perhaps either the decrease in tryptophan concentrations or the increase in chyurinine and downstream toxic metabolites results in suppression of the cancer-killing T-cells. And it's been shown that many cancers express IDO as a way of suppressing the immune system. And patients whose tumors are expressing a lot of IDO1 have a poorer survival, a poorer prognosis. So it's a no-brainer, really, that we should try and develop drugs that block this enzyme, and then we could use it to restore the activity of the immune cells that kill the cancer. And we and many other groups have been trying to sort of do that. Now, so next door, next to the toilets, I had a team. We developed assays that allow a team of students to sift through as many compounds as they could to look for IDO inhibitors. And we actually went through over 40,000. And we got quite a few, 228, but not every single compound can be converted or is suitable for conversion or use as a pharmaceutical. We needed compounds that could get into cells because IDO is an intracellular protein. We also did not want the compound to be cytotoxic and kill off the immune cells or other normal cells. We wanted the compounds to have good metabolic stability so it's not converted quickly to a useless compound as soon as you give it to patients. And we certainly wanted ones where you could give as a pill because it's so much more convenient than asking your patients to come in for intravenous infusions. And once we'd sort of put all the compounds through all these tests, we ended up with about three. But the most promising ones has been licensed to a biopharmaceutical company who will help us take it through into clinical trials. Now, in April 6, 2015, Nature Biotechnology had an editorial saying that IDO inhibitors move centre stage in immunoconcology and chemical and engineering news had the cover on IDO inhibitors unleashing the immune system to combat cancer. Now, I'd love to be able to sort of say that this happened because of the wonderful work we were doing, but unfortunately, no. That was when these two companies started two years after us, but with their deeper pockets and their bigger staff got their IDO inhibitors into phase one trials much earlier. And very soon after that, the big guns, Bristol Myers Squibb and Pfizer had their IDOs in phase one clinical trials. Now, three years later, it's now 2018, where are we? Where are they? Well, New York's genetics was the first one to withdraw, and we still don't know whether it's because the IDO inhibitor didn't work, or Genentech's immune checkpoint blockade, which was untested at that time, didn't work. But we weren't worried because the polka-dose stat was burrowing along and was in phase two and getting good results. But then early this year, Pfizer stopped recruiting patients with brain cancer for use with their IDO inhibitors. They had only recruited 19 and decided to stop, which I thought was rather strange because normally one doesn't expect much in phase one trials with a monotherapy. But the polka-dose stat was still burrowing along, and this time in phase three trials in combination with Merck's anti-PD1. But when in April 2018, they announced, Merck announced that they were no longer continuing to go ahead with Insight's IDO-1 inhibitor. It did put everybody in a bit of a spin, and very soon after Bristol-Meyer's squib, just a couple of weeks afterwards, decided that they would stop recruiting for their phase three trials of their in-house IDO-1 inhibitor in their in-house immune checkpoint blockade. Bristol-Meyer's squib had just recruited 72 of the 700-R patients that were hoping to put onto the phase three trials. But both Bristol-Meyer's squib and Insight are not saying they're just taking a breather. So they can sort of go back and analyze all the subsets in their phase two trials, which had very good results, and they just want to analyze the patients that did respond so they could find the markers of selecting ones that will respond versus those that don't, and make sure that going forward, they can route the ones that will respond. We at the same time have also put the trials of our IDO inhibitor on hold, and at the moment we're back in the lab, trying to understand more about the relationship of IDO-1 and TDO, because the body has two enzymes to do the same pathway of converting tryptophan to chineurinine, and we had preclinical data that suggested that when we used IDO-1 inhibitors to inhibit IDO-1 to cure cancer, I forgot. Well, the increase in tryptophan sent a feedback message to the liver, which expresses the TDO, and it's TDO who's responsible for the normal homeostasis of tryptophan and the blood encirculation. And so when the liver gets the message to increase the IDO activity, then it converts tryptophan to chineurinine and just counteracts the effect of the IDO inhibitors that we want to reverse, to restore anti-tumor immunity. And if this is what's happening, then IDO inhibitors on their own may not be effective, and you need to perhaps be giving an inhibitor of TDO at the same time, and it just so happens, we have in the lab some lovely IDO selective and dual inhibitors of IDO and TDO, and depending on the results of our current laboratory studies, we could, the ACSRC could be in a very good position to be one of the first groups to put TDO inhibitors in into clinical trials. Now am I out of time? Pity. Well, I did want to thank everybody and my funders, the cancer, CSAN and AMRF, and since they get their funding from the generosity of the public, Auckland Public, thank you for your generosity and donations. Thank you very much, Leeming. When we were planning this evening, we were very conscious that it is a winter's night and we didn't want to keep you all too long, we are sticking very much to the timetable, but I'm assured that our speakers will be around at the end of the event, so if you do have some questions, I'm sure there'll be an opportunity to connect up with one of the speakers after the event. So moving right along, next up we have Professor Christon Print, who's going to be talking about genomics for cancer patients. Chris graduated in medicine from the University of Auckland and then worked as a house surgeon in Dunedin before completing an immunology PhD in Auckland. Chris now leads the genomics into medicine program at Auckland University. He's currently Professor of the University's Department of Molecular Medicine in Pathology and a principal investigator in the Morris Wilkins Centre. And I think still very much demonstrating his connection with clinical practice, he's the immediate past president of the New Zealand Society so without further ado, welcome Chris. Thank you very much for the kind introduction and thank you for coming out on such a wet night. My talk's going to be much shorter than Leigh Mings because it's an area that is very difficult to explain easily because it is based in technology so I'll have a shot though. So what I'd like to do is break my talk into three areas. First of all I want to introduce what genomics is and how this disruptive technology of genomics is really transforming our understanding of cancer and moving into transforming patient care. Then after that I'm going to talk about genomics as a way to transform what we can understand about the complexity of tumours and how it's really telling us how little we actually know. Just when we think we know everything, we get knocked off our feet. And then finally I want to talk about the implications for New Zealand patients, people with cancer in New Zealand from genomics. So genomics is a truly disruptive technology. It's the study of genes and genomes, all of your 20 odd thousand genes are the myriad of proteins they make. How does all of this integrate together to make the signalling pathways in cells that Bill Denny and Leiming Ching showed you. The more we study genomics, the more we understand about how cells work but at the same time the more we know we don't understand. I said it's a disruptive technology and it's really technology led. When I went through Auckland Medical School 30 something years ago we didn't learn about genomics at all. But nowadays we use small DNA sequencing machines with the second year medical students who sequence something. Just 5 or 10 years ago we had these massive sequencing machines that took up most of a room. Now we've got ones you can hold in your hand and plug into your laptop or even better ones that plug into your iPhone. This is an iPhone just here with it plugged in the bottom. In a survey that a very talented PhD student, a surgeon, Deborah Wright working with me did in 2011 a very high proportion of cancer specialists in New Zealand predicted that the frequency of use of genomic and similar molecular assays and their influence on their clinical decisions for patients would increase. So there's a really high expectation in the clinical community at least that we have to live up to with genomics. So I'm going to give you now a couple of examples where genomics have transformed something in our understanding of cancer. And this first example is led by my colleague Annette Lasham in collaboration with University of Otago Research, it's led by Anthony Braithwaite and some Sydney researchers. And this is a example where we looked at over a thousand breast tumors and we looked at all of the genes in each of those breast tumors and how they were used by building computer models we were able to work out that a particular protein in these cells called YB1 acted as a trigger that turned on a proliferation or cell division mechanism in these cells. We didn't know this previously. Previously we had no idea how YB1 really worked or rather we thought it worked in many different ways and just weren't sure. YB1 turns out to be a protein or a gene that you can measure in cells to identify the prognosis of patients and we've been very lucky in that using similar techniques to what Leigh Ming has described we've been able to use high throughput screening to get a small number of chemical compounds that appear to inhibit the action of YB1 which we hope may be the start of understanding how to develop a drug. When we did this work we found that in about 8% of ovarian cancers, about 4% of breast cancers, this YB1 gene is so important for the growth of the cancers that it's copied and there's many many copies of the gene. So that's an example using genomics linked with mathematics we call that bioinformatics to really understand the individual molecule. But actually the way cancers evolve they start at individual cells which then divide and get more and more mutations as they continue to grow. And this is a form of evolution in practice. In a study led by Ben Lawrence Mike Finlay myself and several colleagues in the room into neuroendocrine tumors we've started to untangle the whole genome complexity of these cancers. This is a graph just showing how different chromosomes in these tumors have different numbers of copies or different splits between the originally inherited alleles from two parents. In many of these tumors about 25% the tumors appear to be driven to grow not by mutations but by complex loss and gain of whole chromosomes. The same 10 chromosomes appear to be lost in about 25% of the tumors. We've no idea how this works yet. So this is a brand new complexity that we've discovered using genomics about how cancer cells grow. All of this new discovery about how cancer cells grow is leading to us understanding how we can improve treatments. In the graph that Leeming showed you where there was a lot of survival, we want to use genomics to better predict which patients can do well with treatment and in the other patients who don't do so well to be able to identify why the ultimate goal would be to play chess with tumors, to sequence treatments based on the genomic evolution of the tumor but that still remains in the future. In the area of pathology there used to be this phrase where we talk about a variety of different histological or microscopic appearances of tumors and they'd use this to help identify which drugs would be used. And then as genomics started to have an impact on pathology we started to talk about a therapeutic prism and this is an example in lung cancer which Mark McKee is going to talk further about about how different mutations in different genes can help identify likelihoods of responses or resistance to different therapies. These days though we're trying to go beyond this and combine whole genome information to integrate in mathematical models everything we know about a tumor to better predict what drug what prognosis and to match the right drug to the right person. As was alluded to by Bill Denney one of the most exciting technologies is using the sensitivity of genomics to follow cancers through their evolution. I've got a colleague in Otago, Neil Gemel who's sequencing Loch Ness to try and prove once and for all that there is or is not a Loch Ness monster and the reason he can do that is that DNA sequencing is so sensitive that it can detect a few molecules which presumably have a Loch Ness monster specific DNA sequence in the whole Loch. Well we can do the same thing in the much smaller Loch of the human blood. And this is a slide from a project led by Sandra Fitzgerald Rosalie Stevens, John Matthews and several other clinicians in Auckland where we're trying to follow patients through the immune checkpoint inhibitors that Leeming Ching told you about to identify whether patients are responding or not very early on and this is following through three courses of these checkpoint inhibitors and sadly this is an example of a patient who is not responding. As these graphs are trending upwards this is telling you that the amount of mutations that have leaked out of the tumour into the patient's blood is gradually increasing as the tumours continue to grow despite the therapy. So I'd like to conclude by first of all reiterating that this disruptive technology of genomics and all the computer work that goes with it is truly transforming what we know about cancer but it's also telling us how much we don't know. The major limitation to how we can use genomics in the clinic is how much we don't know about genes and proteins in ourselves and this is why basic fundamental research such as is funded by the Cancer Society ARMRF and many others remains critically important. We've not solved cancer. We've just learnt how much more we need to do. The second point I wanted to make is that genomics is genuinely beginning to guide precision oncology. Patients are genuinely starting to benefit however there's a few inequities creeping into this as a rather socialist person I'd love to see the democratization of genomics and genomics being freely and equally available. One of the ways that we're hoping to be able to do that is with some of these new technologies like measuring circulating tumor DNA measuring mutations in patients blood can be easily done on a Marae clinic or away from a hospital and we're hoping that this isn't another perpetrator of inequity in health in New Zealand but rather these technologies can actually reduce inequities. Thank you very much. Thank you Chris, a lovely talk. Any questions from the floor? I think that's probably a lame-in question. Do you want me to hand it over to you? Give it a go Chris. This is a adoptive cell transfer approach. I understand thinking of the right paper and I think the main challenge with it is to use technologies like genomics to identify why this is working in some patients and not others. Professor Rod Dunbar in Auckland is working up these technologies in New Zealand we're very lucky that we've got a very active research program into these technologies here. Thank you. We will move on for the benefit of time so thank you very much Chris for your talk. It is an distinct pleasure and honour to introduce Professor Bruce Bagley, distinguished Professor Bruce Bagley. Bruce grew up in Hamilton and initially as a chemist but saw the light and moved into biology. He then did a postdoc after his PhD in Auckland did a postdoc in Switzerland and returned in 1968 to work at the Auckland Cancer Society Research Centre. Since that time he's either been director or co-director. Someone's phone. And Bruce his major research interest has been in the development of anti-cancer drugs where comprehensive laboratory studies can be complemented by clinical trials in cancer patients. So with that introduction I'd like to welcome Bruce to the podium. Thanks Mike and thanks everybody for being here. Can everybody here? Okay. Makes it even better. So this title of this talk was actually not my idea was somehow got transposed but then I started thinking about it and thought well actually it's quite a good quite a good title because as you see from what I want to talk about this really makes sense. I want particularly since it's 50 years from the start of the medical school to go back in time a little bit because the year the medical school started here was also the year that I started with Bruce Cain's team and Bruce was not only an amazing medicinal chemist but he had a real concern for cancer patients and trying to develop new treatments for cancer which at that stage was quite at quite an early stage so he one of the first things he did for me was to introduce me to a clinician John Buchanan who is a hematologist and John when I talked to him said that one of their problems was that they had a new drug, exciting new drug for treating leukemia but it only worked in some patients not others and so was there a way of picking in advance which patients might respond and which patients don't respond and since it was a blood condition perhaps we could get a blood sample which is quite easy to take hopefully most patients easy to take and we could use that to decide whether the patients might respond or not. Now I want to talk about this the actual project because it was quite interesting but one of the things which was important for me personally was that I got to talk to patients so we would go every week to the hospital and collect blood samples for these studies and so for the first time really in my career I got to talk to a lot of cancer patients about what their views were and what their aspirations were and one of the things which struck me particularly was that they wanted to help other people so a lot of their willingness to provide samples and so on was aimed at helping people in the future and so I was quite inspired by the people that I met at that time and it shaped my career since then. Now I want to leave for a little bit now because it's probably another 20 years and over that time there's a whole lot of technological advances in how we could look at cancer cells and the kind of equipment in the lab was changing and not only that we had some good people that were arriving Graham Finley joined the group and he was an expert on cell culture and a very good person to have in the lab John Matthews was an enthusiast for cancer treatment who was a clinician and wanted to see how we could bring ideas from the lab back to the cancer patient so we're in a good position to do that and we thought that one of the things we'd like to do is to take a sample when a patient had surgery for other types of cancer take a sample and cultured in the lab and then find out by exposing those cultured cells to different drugs which one was the best one for the patient and we could go a little bit further and say well if we had those cultures we could use those to assess new drugs that were coming out of Bruce Kane's program so this would have a double advantage in a way if we could make that kind of system work well in 1989 we had some good luck in a way because we employed with the help of funding from the Health Research Council we employed Elaine Marshall to do this and she was not only a very excellent person for getting these cells to grow she had sort of green fingers for this but she also knew how to talk to patients and get their permission because we needed ethical permission for all this she knew how to talk to the theatre nurses and so on so the samples from the surgery came to the lab rather than being thrown out she talked to the surgeon and pathologist because all of those people had to be involved in this whole process and so she was real gem as far as this project was concerned and behind her we had another person Wayne Joseph who's still working with us in fact who acted as a fantastic backup person who could do those things as well so we're very lucky to have that kind of system going so what do these cells look like once they've, we get them from surgery and take them into the lab the first thing we do is to actually cut them up into very small pieces because they have to be apportioned out to various tiny tiny cultures and so this picture here is probably magnified about a thousand times and each of these little clumps have got several hundred tumor cells and if you go one further and this is now another hundred times further magnified so something like a thousand fold magnification you can see what looks strange it's forgiven for thinking it looks like spaghetti and meatballs but the spaghetti is actually fibers like collagen which form a kind of a nest for the tumor to grow in and the grey parts are the tumor cells themselves now one of the problems when we take this tissue from surgery and mention I cut it up into tiny bits that induces a reaction called a wounding response as you might imagine if you take a piece of tissue and chop it up it's going to cause a lot of physical damage and the body reacts to that by certain cells that start dividing to try and repair that damage and so you've got to be very careful when you are doing this you end up looking at the response rather than the tumor itself so we have to differentiate those things and Graham Funde found a nice way of being able to suppress the wounding response so we can actually just look at the effects of the cancer cells themselves it's actually not a robot the other end of this is Wayne and the reason is shaking a bit is because I'm on the camera but this is a type of manipulation that we had to do hundreds of times over to apportion these cells and tiny amounts into these little microcultures so of the many hundreds of patients this is just a selection so you can see that there are many different types of chambers that we've got samples from and many different surgeons that were involved in these projects and these are just some of the surgeons and this is a project which is still going on and we're just sort of completing it now but it's been going for 30 years it's a long project and you can see how you need to have a large number of samples in order to really find out what's going on and one of the things we looked for we thought we would grow these cultures that we might find for a particular patient when we grew these cultures that those cells were really responsive to one of the drugs and they didn't work with others and so in that way we could say this is the drug that we should use for that patient and for another patient another one would light up and we could use that one but it didn't really work out the same like that we found that there was a tendency when we got a sample from a patient that either it was sort of sensitive to everything or it was resistant to everything so what was going on that we could get a picture like that it took us a long time to understand what was happening and the result was that these different cultures were actually growing at different rates and we found that the growth rate in culture related to what was going on in the patient as well and we went further than that and had to get involved with sort of mathematical modeling and so on and people with mathematicians try and work out on the patient basis what was going on so it's a long process but it was a very interesting set of results because we found things that we hadn't expected before now I just wanted to stop a moment and talk about what's in cancer tissue because you sort of think of cancer tissue as being just cancer cells in fact there's a lot of different cells in there and doing different things so apart from the cancer cells and this fibrous little nest for the tumour and the fibroblasts that make that nest there's also a blood supply and you can see in this picture here there's a coloured red cell here and this is the capillary containing the blood supply for that particular tumour and also you have immune cells that Lamangas talked about but also you have what might call a sanitation system you need cells specialised that dispose of the corpses of the dead tumour cells and why do you need this well I might just start with the question of how fast a tumour grows in a human how long does it take for a tumour to actually double its volume and it might be surprising to you to find out the time taken to double the volume of the average human tumour is about four months so it grows more slowly than we perhaps give them credit for some tumours will grow faster than that and that means if you think about the mathematics of this is that you can find out that individual cancer cells double their number in about a week but the tumour itself doubles its number in about four months and this means that there is a cell death going on it's not all of the cells from the tumour continue they are dying off at quite a rate and this is a process called turnover and you can sort of think about that or you can talk to an accountant who knows all about turnover it's the same sort of process though but it's possible just to ignore this and say well the cells die and that's all we'll risk to it and that different tumours have different rates of turnover so different numbers of dead cells are being formed and transported away by the sanitation system but why is that important it's important because dying cancer cells themselves send out a signal which is effective on the whole immune system and so dying cells make a signal to the sanitation system cells that tell it to eat it up because that's the way that these cells got rid of because other cells eat them up but depending on how many you have the system can get pushed in one direction or another so if it's on a sort of an active phase then this system actually works together with the immune system that Lamming was talking about and getting rid of tumour cells recognising and getting rid of them if it's being sort of overloaded it goes to another mode called wound healing where it's really primarily concerned with mopping up the damage and it actually suppresses the immunity so that's a really important area if we can understand that perhaps on some tumours they're sort of exhausted as far as their immune properties are concerned and they stop working properly so in fact Stacey on this on the other side is a student from here who's now working at the University of Bergen in Norway and she's really interested in this area and particularly in the vitamin K seems to be involved in this process as well so if we could manipulate that and help to turn the immune system back on again we have a really important area to develop as far as cancer is concerned and the next steps is a personal one for me because in 10 days time I'm going on leave and going to be working in this lab in Norway on exactly this problem and trying to understand what is going on and what is interesting here is that the group in Norway have got a new drug which works exactly in this area and it's a clinical trial at the moment and the results so far are promising so this is a new direction in a way of finding out new ways and you might notice among the talks that we've had so far there are many different approaches to the same problem so that's what I'm going to do and then come back here towards the end of the year so in summary this is a picture an impressionist picture dealing with pointillism I suppose Sarah I think is the artist but the point here in this picture is that it's made up of a large number of tiny little coloured patches but when you start to put them all together you see a bigger picture and I think this is what we feel with this culture system that hundreds of patients have provided samples we've collected data and we can collect more data using techniques like what Chris has talked about and gradually pick up a picture of what is really going on in human cancer at the body level just to finish I'd like to thank particularly the cancer patients because there's been very many of them and they've all contributed to this picture and their contributions will carry on into the future it's involved a large number of surgeons and pathologists nurses to people in the hospital and as well as that of course all the people behind the toilet as Le Ming has mentioned that are working in the cancer lab and they've all contributed so I'll stop there and thank you for listening we've probably got time for one question perhaps perhaps my question Bruce would be that I've often heard it said that you talked about going all the way up to Norway the other end of the world or down in this part of the world a little on New Zealand that New Zealand really punches well above its weight in terms of its prowess in terms of research would that be true? well of course the lab in Norway came to us in a way because they recognised us as a leader as well so it's a two way thing it's not that the lab is superior to ours it's really a discussion from two different points of view and two different backgrounds and I think that's the sort of enriches cancer research when you work together like that so it's not one versus the other I think it's both working together and building on the legacy we've had by growing all of these cancer cells from patients that can now be useful for other studies in different countries alright now ladies and gentlemen it's a real pleasure to invite Professor Keke to give us a talk on personalised medicine Mark is a physician scientist with many years experience as a research group leader he's also a practising medical oncologist clinical trial investigator a teacher of pharmacology, oncology and clinical medicine with over 100 research articles and 3,500 citations published which finds time to be a professor in the Department of Pharmacology and Clinical Pharmacology and co-director of the Auckland Cancer Society Research Centre ladies and gentlemen Mark McKee well thank you so good evening and personalised cancer medicine what has it achieved against New Zealand's biggest cancer killer is the biggest cancer killer in New Zealand as shown here by this data from the Ministry of Health so lung cancer is the leading cause of cancer death accounting for about 20% of all cancer deaths so this is the death percentage caused by lung cancer ahead of the other major cancer killers in New Zealand colorectal cancer, breast cancer prostate cancer and pancreatic cancer lung cancer is the fifth most common cancer registered in New Zealand it accounts for about 2,000 cases of cancer each year and it unfortunately has poor survival so only 30% of lung cancer patients will be still alive one year after diagnosis so our society stigmatises people with lung cancer possibly because of its association with death and smoking and these negative attitudes towards lung cancer are scientifically proven in research so formal investigations such as shown here which investigated comparative attitudes to breast cancer versus lung cancer showing that attitudes are much more negative with concerning lung cancer than breast cancer so but smoking habits have changed greatly in New Zealand so currently 60% of our population are never smokers 5% are former smokers and only 15% are current smokers so if this room was representative of the New Zealand population perhaps the people in the middle between the two aisles would be the never smokers the people all over on the right here on my right maybe they are the former smokers so they no longer smoke but have smoked over 100 cigarettes in their lifetime and the people on my left over in this aisle are the current smokers who are struggling with their dirty habit so but there is hope from new personalised approaches to lung cancer treatment so personalised treatment involves the identification of molecular drivers of lung cancer in each individual patient and then using that information to individualise their therapy it involves no longer treating lung cancer as one disease but a series of individual diseases and treating it accordingly it involves collecting a specimen of the lung cancer prior to treatment and undertaking an analysis of that tissue about its genetic make up and the gene expression to understand to try and identify the key driver of that cancer particularly those drivers that can be disabled by a specific drug treatment so within the last five years these personalised lung cancer treatments have been introduced into the New Zealand healthcare system and so with others I've been studying the uptake of these new approaches and the impact they have had on lung cancer in New Zealand so epidermal growth factor receptor or EDFR mutation positive lung cancer was the first molecularly defined subtype of lung cancer for which a personalised treatment became available in New Zealand so between 2012 and 2015 PHARMAC funded a lot in Abangaphitanib which are EDFR inhibitors for use for treating EDFR mutation positive lung cancer and at the same time the Ministry of Health published guidelines for the testing of lung cancer for EDFR mutations and so we've been studying how well these new treatments have been implemented in our healthcare system and found that the uptake of testing has increased with time up to to reach testing of 75% of patients who are eligible for testing and that's about the highest rate in the world so we're doing pretty well on a global scale also we've been able to understand how prevalent EDFR mutation mutation positive lung cancer is in our population so the prevalence and the tested population is about 22% so we would estimate that would be about 300 patients per year will present in New Zealand with this molecularly defined form of lung cancer it has also challenged the stereotypes about lung cancer so it's enabled us to look at the smoking status of patients presenting with lung cancer who are eligible for this testing and so which surprised us because most of the lung cancer patients are coming from the group over on our right the former smokers that's the orange bar there and then the next most common, most patients come from the current smokers but almost the same number of patients come from the middle group the never smokers so this is really challenged the stereotype that lung cancer is a problem of them the smokers it's really not in our society and our research has also allowed us to study the impact that the introduction of this testing and targeted therapy has had on the survival of lung cancer patients shown here so comparing patients who were untested who have relatively poor survival compared to those who are tested and are found to have an eduphal mutation in their tumour and can be treated with one of these drugs and even the patients who are tested and have no mutation have better survival compared to those who are not tested so testing is associated with improved overall survival irrespective of the result of this testing. So anaplastic lymphoma kinase gene rearrangement positive or ELK positive lung cancer is another molecularly defined and highly treatable new lung cancer subtype so this ELK positive lung cancer was discovered in Japan in 2007 and in 2015 the very first treatment for specific treatment for lung cancer was approved by MedSafe in this country so for use in New Zealand but here in 2018 we still have no Pharmac subsidised treatments or national testing program for identifying patients for with ELK positive lung cancer but in our research we have been trying to learn about the prevalence, the profile and outcomes of ELK positive lung cancer patients in our population so what is surprising despite the lack of any Pharmac subsidised treatments clinicians are still doing a lot of testing they think it's important to identify these patients and so over 350 patients have been tested in northern New Zealand for ELK positive lung cancer so this has allowed us to estimate the prevalence which is 8.5% of tested patients which would mean in New Zealand there will be each year over 100 patients present with ELK positive lung cancer we've also been able to look at the profile of these patients and it's surprising again challenges the stereotypes ELK positive lung cancer patients are young, most are less than 60 most of them have never smoked and they're more likely to be Asian Pacific or Maori and ELK negative who are mostly Caucasian and we've also been able to look at the survival outcomes of patients with ELK positive lung cancer in the absence of any Pharmac subsidised treatments so for patients who unfortunately have been unable to access any specific ELK treatment through a clinical trial or access scheme their survival is as we would expect for lung cancer so most patients die within one year of diagnosis whereas for those that are able to access ELK specific treatments through clinical trials or access schemes 90% are still alive two years after diagnosis so a dramatic difference in survival outcomes meaning that once we get round to implementing ELK testing and targeted therapy in New Zealand this will greatly improve survival so the final sub-type of lung cancer I'd like to briefly talk about is that it's defined by its strong expression of a protein called PdL1 and it is highly sensitive to immunotherapy with so this is personalised immunotherapy for lung cancer and program cell death like N1 is expressed on tumor cells and helps the tumor cells resist immune attack but it's very variably expressed between different patients so some patients have tumors that have very little expression, other patients have tumors that have a lot of expression of this PdL1 and what we know from clinical trials elsewhere is if you select lung cancer patients with very high expression then you're selecting a group of patients that benefit a lot from Ketruder treatment and this is a clinical trial of Ketruder and PdL1 strongly over-expressing lung cancer and in this trial Ketruder more than double survival has less side effects but unfortunately is more expensive currently we have no local data on prevalence or profile of PdL1 strongly expressing lung cancer in New Zealand and we have no testing guidelines or state subsidized treatment so I'd like to finish by urging you to support these strong advocates of lung cancer prevention and treatment so firstly the Lung Foundation who are a new group and are doing important work advocating to the government and others for better access for lung cancer patients to treatment and care recently the Lung Cancer Foundation approached the health ministry officials about the parlour state of lung cancer treatments in New Zealand and those health ministry officials then transferred the health of the Lung Foundation on to the minister of tobacco so the problem with attitudes to lung cancer go right to the top so it's perceived in our government as a tax issue rather than a healthcare issue and also the cancer society who have and continue to do really important work in striving towards a smoke-free New Zealand thank you thank you Mark for a wonderful talk any questions from the floor it's because the question was why do such a large number of lung cancer patients people get lung cancer and are not smokers it's because there's a significant proportion of the total amount of lung cancer that is not related to smoking these are the forms of lung cancer that we now recognise have specific molecular drivers like EGFR or ELK smoking does not play a role in the cause of those types of cancer these will become increasingly important because smoking will eventually die out from our society and that means that the lung cancer burden and former smokers will eventually disappear from our society and that means that the lung cancer burden will be from never smokers one more question the question is is small cell lung cancer a subset of lung cancer as you're describing this evening or is it a separate cancer small cell it's a subtype of lung cancer overall it probably accounts for 10 to 15% of all lung cancer it is becoming less common as smoking becomes less prevalent and in our society well that's a good question I don't think we know thank you Mark well answered there's always questions that we can't answer so on that note I'd like to introduce our next speaker thank you Mark Professor Mirren Gott Professor Gott has had 20 years of experience in conducting research within the older population and with interest in developing models of palliative care and end of life care Mirren is a director of the TRI palliative care and end of life research group and that conducts research in a multidisciplinary biocultural setting using creative social research methods to inform practice and policy and we're very much looking forward to a talk which will be quite a different switch from what we've been talking about but welcome to the panel thank you very much good evening everybody it's great to have this opportunity to tell you a little bit about the work of the TRI palliative care research group and it's late and I'm hungry so rest assured I'm not going to take up too much of your time and I'm also going to talk about something that we all know something about and that's caregiving so Rosalind Carter, former first lady and she's now a care activist says there's only four types of people in this world those who've been carers those who are caregivers those who will be caregivers and those who need caregivers so essentially we all have a vested interest to get this right I want to talk about caregiving within a particular context and that context is palliative care because despite the sterling of my colleagues I've got bad news for you and the mortality rate is still 100% so we still do need palliative approaches to care and this is an approach to care for anyone with a life limiting illness so our work includes cancer but is not exclusive to cancer and we also know that palliative care can actually not only improve quality of life but it can also extend life and that was a trial done with people with lung cancer in the States so critical to the discussion that we're having today it can also significantly increase quality of life for caregivers and I should say that in New Zealand you can either receive palliative care through a specialist service about a third of people will receive it that way or via your usual care provider very often your GP just another point of context these are figures produced by a member of my group Heather McLeod for the Ministry of Health looking at need for palliative care the big home message is that within the next 35 years the need for palliative care is going to almost double and this is huge and within the context of what I think were euphemistically calling a constrained health system it means that more and more work is going to be put onto family caregivers and the nature of this work is becoming much more complex we know that being a caregiver can bring benefits and I want us to remember that but I also want to talk a little bit about the costs it can bring psychological, social and what I particularly wanted to mention is financial because it's something we don't really talk very much about but I'm really keen to further explore the financial costs of caregiving because unless we know those the economic analyses that we conduct actually exclude all the costs that are incurred by caregivers so we say well you know we can reduce hospitalisations and this saves the health system money but what those sorts of analyses don't recognise the health money is being put onto families and so we explored this within the context of Auckland and I just wanted to tell you one story because I think our work makes us social activists and makes us want to create change and this is one of those stories that stays with you and this is two sisters we spoke to whose mother was dying in Auckland hospital and they couldn't actually both sit with her at the same time because they couldn't afford the parking so you know it's really shocking that these are the sorts of situations that people are living with and as I said it's these sort of stories that keep us going and motivated in our work to create change what else do we know? Well we know that family caregivers spend approximately 70 hours a week caring in the last three months of someone's life so it's a huge amount of work however they often struggle to access the supports and information they need and I'm sure those of you here who have been caregivers will find some benefits with this and particularly with the fact that caregivers are having to navigate a really fragmented health and social care system and we talk a lot about professional care navigators but often with the lack of recognition that families are actually often out there doing this work already but they often feel unsupported by health professionals and health systems which is so siloed, our health system is so siloed and it's family caregivers that are often there trying to put the pieces of the puzzle together but I didn't want to send you out into this cold dark night feeling a bit depressed about the state of things I wanted to finish by saying a little bit about what our research is doing to make a difference so firstly our research has been critical to informing new policy directions by the Ministry of Health so there was a new palliative care action plan announced last year and for the first time there's a really significant focus upon family caregivers it's one of the five priority areas and our work's been really instrumental in underpinning that shift in focus but we are not naive enough to think that policy in itself creates significant change there wasn't any targeted money put against this policy so we also work a lot in partnership with lots of different service providers there's lots of different people working in this space so we work with DHBs we work with the aged care sectors group for us, we work with communities and we work with NGOs as well and just to mention one project we're currently working with colleagues at ADHB and they recognise that the one area of patient experience they don't know anything about at the moment is what's happening at the end of life so we piloted a questionnaire that's being rolled out now across ADHB we've got over 600 family carers who've completed that and that's for anyone who's had a contact with ADHB in their last year of life and what's looking really positive is that ADHB are keen to pick this up as a routine service improvement measure so for the first time we'll actually have experiential data from the people who are most affected to actually inform policy and service development and already there's some really interesting stuff coming through and the palliative care governance group are looking at how those changes can start to be made education and training, we're in university so all our research is directly feeding into education and training within the School of Nursing we have palliative care as a thread that runs throughout all our curricula we also have specialist programs and we also feed into public debate and to do this we're very aware that research can sometimes be a bit dry and boring so we look at creative ways of getting our research out there so for example our last HRC project we actually worked with colleagues at the Faculty of Arts and we made a film so we had actors talking to the narratives that people were telling us the stories they were telling us and this is being used as a resource for training GPs for example and it's also being used within communities to have conversations so lots of the issues that we find out about actually don't require a huge amount of resource to fix and one thing that we're trying to do all the time is to look at where we can actually do something that will make a big difference but there's not huge amounts of money in this space so what can we do with not very much so we're starting to create a lot more resources for caregivers so for example together with undergrad nursing students my colleague Michael Boyd has just created a resource for people around choosing an aged care facility so aged care facilities are actually the most significant providers of palliative care in New Zealand at the moment particularly if you're a woman so we're really looking at how we can make palliative care better in those settings and these sorts of resources you know the sorts of things to look at when you might want to choose a facility are the sorts of things people have been telling us that they want to receive finally but probably most importantly we're working alongside caregivers and alongside communities to help them identify what supports they want and what can be put in place from their point of view so for example the group on the right of your slide they're community collaborators and Komatoa from a new project led by my colleague Tess Moica Maxwell which is funded by the HRC and that's looking at how Maori end of life care practices can be gathered that information can be gathered because this was something our Komatoa felt was being lost and it's going to be used to create a digital resource so Fano can access that information when they need it we also supported this lady here who's an amazing activist and she wrote the first practical guided caregiving that was written actually by an ex caregiver and then finally at the bottom we worked with the Pacific community and this is why it really pays to actually ask people what they want because I think we went in thinking oh well they probably want some sort of information, leaflets or maybe some educational sessions but what they actually wanted and this was a group of older female caregivers to create a music video so they actually got a local rap group to create a music video and if I had time I'd play it for you but I don't but it's fantastic and I never thought that in my research career I'd produce a music video but probably the most exciting thing I have ever created in my research but what's great is it's being used within Pacific communities, within churches to actually spark a debate about the sorts of support that caregivers need so that is all I wanted to tell you tonight so thank you very much for listening, I'd like to acknowledge the rest of my group, there's about 12 to 15 of us, we're a very multi-disciplinary team and also all our research participants we speak to people at what is often not a very easy time of their lives but I think as Bruce said earlier people really want to give back and they really want to tell their stories but we're very grateful to them for doing that and thank you for your time this evening I just wanted to ask everyone what is the current time lag between the end of clinical trials when something is available and when members of the public who have cancer or looking for it can expect to find it it's the first part is there an average length at the moment or does it vary widely because I guess I asked that because we've got a grandson who had leukemia but the gap between the knowledge that Judy and I as university staff members can access and the clinicians who are treating them and the other people working with them are so big that we found ourselves resourcing and supporting and arguing and fighting and so we would like better information service available to people and we'd like that funded actually as a research project how to provide better information services to people about what's happening in cancer is wonderful to be here tonight and hear what's happening but for lots of us this is the one off so if you could do anything about that it would be great did you pay for the parking no I wish we could have done but actually this was retrospectively so they were telling us this story but yeah I've been thinking about creative ways to do something about that that's on my radar so if anyone's got any ideas how's it brilliant that's fantastic I'd love to hear more in terms of access to healthcare and in this case palliative care there tends to be a huge like social economic basis to bias and basis to it as you said in the news article about the two sisters who had to sleep in the car so I was curious as to what you and your group or any other groups are doing to like work on reducing this inequality between say like people of different like social economic classes or other like inequities in New Zealand yeah thank you that's a great question so one of the big focuses of our research group is equity so the way we do that is firstly by primarily concentrating on people who don't get access to specialist palliative care because we know that they have a much more difficult time and we also work really closely with different cultural groups to look at specific needs and we're always very sensitive to issues around economics and we're just about to write an HRC grant which is going to look at hopefully probably won't get funded but fingers crossed would look at palliative care provision in economically deprived communities using an asset based approach so looking at kind of what assets they draw on and then from their point of view what the challenges are because I think that's always the key is to look at the strengths and to look at what people on the ground really want rather than guessing but thank you it's a good question one more question a lot of these people will be older and actually the system probably doesn't want us living longer because I'm just wondering how it kind of balances out how you you know what I mean I mean you're right the biggest growth in palliative care need is for people over 85 and it's for people with complex comorbidity so what we really need to do is actually to understand a bit more about the sorts of care people need in that situation because our models of palliative care are based on younger people with cancer so we need to, for example as we are looking at how to improve palliative care and aged care because that's a huge setting for palliative care if you're a woman and over 65 you've got a more than 50% chance of dying while you live in aged residential care ladies and gentlemen that brings us to the end of tonight's program and I just wonder if I could invite all our speakers to just stand up for another round of applause please I'm very conscious of time so I thought but I was given the challenge to try and sum up tonight in two minutes so I'll have a go at that see what we can do because tonight really was a bit of a smorgasbord a sort of a degustation menu of incredible science Bill started off with a very uplifting message around the technology behind some very exciting new drugs that are coming our way and I think the very the great signal there that cancer survival rates have more than doubled since the 1970s it still shows us we have a long way to go but I think we get a sense that we are making great progress each and every year Lei Ming then put the frighteners on us talking about killer T-cells serial killer cells and then weapons of mass destruction but when you think about the context of all of that it sort of makes great sense and how she detailed how our own immune system can be channeled to fight our own cancer Chris was very much the modernist he used the phrase disruptive technology and talked about playing chess with tumours how science can and understanding the genome the genomes and tumours can outflank and outsmart them and we can now get our targeted medicine and then there was Bruce and what we didn't know about Bruce was Bruce plays the cello he's a very accomplished cello player and his message was very much one of culture growing cell lines in culture and translating his laboratory research into trials with patients and we learnt that you need green fingers to do that work so I thought that was good Mark's message was one of great compassion for those in our community with lung cancer who, yes it is true are often stigmatised because they have lung cancer and we need to be very compassionate and I think Mark illustrated that no two cancers are exactly the same and we can get very much personal if we understand them better we can get very much more effective and personalised medicine and then I think Maryn finished things off very nicely with a refreshing dare I say a very caring approach to the subject that we don't really like to think very much about which is palliative care, end of life care what happens to us in that last stage and this is really really important work because I think as you say we'll all be caregivers and needers of caregivers at some stage so look, thank you again for our speakers, I thought it was a fantastic event it's great to get these small tastes of what's going on I know our speakers will be staying around so I'm sure please feel free to interact with them, you'll have other questions and I'm sure they'll be only too happy to talk to you after the event in the foyer and just as a final word for me, a commercial for the next event that we're having here which is on July the 19th and Mayor and you'll be very pleased that this is called Living Longer, a social revolution so that's at 7 o'clock July the 19th I believe it's in the same place so we'd love to see as many of you as possible coming along to that and please spread the word about these events, the fantastic events and the more people that can attend the better so thank you very much for coming along and a safe journey.