 If you look across all clinical trials in cancer, about 97% of drug cancer pairs that go into clinical testing failed in clinical trials. And this extremely high rate of clinical trial failure suggests that there are certain ways in which the characterization of cancer drugs and cancer drug targets can be improved. This is particularly relevant to the question of precision therapy in cancer. So precision therapy is this idea that we should be able to analyze a patient's tumor, find a specific genetic change in that tumor that we can then go on and design a very specific drug in order to kill that tumor and to kill nothing else. So for precision therapy to work, we need to have a drug that specifically targets something important in cancer cells. And we wondered because of some previous research that we had done and because of this 97% failure rate whether there were problems with the design and the development of very specific anti-cancer agents. So what we did is we chose 10 different anti-cancer drugs that are in various stages of clinical or pre-clinical development. And what we wanted to do is we wanted to see if these drugs worked how they had been advertised to work. A lot of these drugs and drug targets were initially characterized using the best technology from 10 years ago, which is a technique called RNA interference which you can use to knock down specific genes in a cell of interest. And using RNA interference, several proteins were reported to be essential for cancer. There are certain proteins that drives a cancer's growth. And over time, a cancer just becomes so dependent upon this protein that it's kind of like addiction. When we looked at these same proteins using what I think could be called the best technology from today, which is CRISPR mutagenesis, we were very surprised to see that when we eliminated these proteins, the cancer cells were actually fine. These were proteins that were supposed to be essential for cancer, but we could get rid of them and the cancer cells didn't care whatsoever. That was surprise number one. Surprise number two was that when we took these cells that no longer express these proteins and we gave them the drugs that are supposed to inhibit these proteins, the drugs still killed the cancer cells. So what this suggested is that these drugs, these putative precision therapy agents are actually killing cells in an off-target manner. They have some other way of killing cancer cells that at the time we didn't know about. So we wanted to see if we could figure out what some of these anti-cancer drugs were doing. So we took one drug and what we found is that it targets a protein called CDK11, which has never before been targeted in cancer therapy. And so I think that in part this work is a story about technological evolution. Using CRISPR, which though it has its downsides, is in general more precise and more specific than the RNA interference technologies that were used previously, we can get a more accurate answer and we can do a better job of figuring out what's actually essential for cancer cells to divide. And if you know what a drug is actually targeting in cancer cells, then that can help clinicians identify the patient populations most likely to respond to a particular therapy. And that's the overall goal.