 This new finding comes from a research article that was published by Ronald de Pina's group at the Dana-Farber Cancer Institute in the M.D. Anderson Cancer Center. This publication is titled, Passenger Deletions Generate Therapeutic Vulnerabilities in Cancer, and was published August 2012 in Nature Journal. The authors of this paper were motivated by the idea of personalized medicine, providing more targeted treatments for individual cancer patients. Cancer is a condition where cells grow and divide in an uncontrolled way, forming tumors that can be lethal. So what are current mainstream methods for treating cancer? The current method is chemotherapy, which kills all dividing cells regardless of whether or not they have cancer at all. So as you can see, this is a pretty brute force approach, and we still have a long way to go before we can understand exactly what drives cancer cells to the point of uncontrolled growth and how we can stop it. To understand exactly how cancer cells behave, let's turn to the DNA sequence of cancer cells. Cancer cells acquire the ability to grow indefinitely due to changes in their DNA sequence which we call mutations. One type of mutation that can occur causes the deletion of a large chunk of the DNA sequence. So why would a cancer cell want to delete part of its DNA? That sounds like a terrible idea. Well, DNA provides the template for the synthesis of proteins. Some proteins promote growth of cells, and other proteins prevent cells from growing too much. So you can see that it would be advantageous for a cancer cell to get rid of proteins that prevent cell growth, so as to allow the cell to grow and divide longer. Cancer cells do this by deleting the DNA template that makes these anti-growth proteins. We call these types of proteins tumor suppressors because they prevent tumors from growing. These types of mutations are often found in colon, breast, and lung cancers, for example. But often times when cancer cells delete tumor suppressor templates, they also delete the DNA around that provides the template for other proteins. We call the deletion of these other templates passenger mutations. So now that you understand how certain cancers develop upon deletion of a tumor suppressor, let's turn to the finding of this publication. Most people studying mutations that arise from the deletion of a tumor suppressor focused on the tumor suppressors themselves. But what these others did differently is they focused on the other templates that are deleted along with the tumor suppressors. The loss of these other templates and the proteins that they make does not contribute to causing cancer. The loss of the tumor suppressor is the only thing that causes the cancer cells to grow. So from a therapeutic standpoint, how can we use these passenger mutations to treat cancer? Well, it turns out that these templates that are accidentally deleted along with tumor suppressors are actually part of protein families, which are groups of proteins with redundant functions. So in this case, let's take the Analyze protein family. This protein family is made up of two proteins that come from two different DNA templates. And these proteins all play very similar or redundant functions. In order to survive, the cell needs at least one of the two members of the family to be present. So let's try to understand what this means for cancer cells. If a cancer cell has accidentally deleted one of the members of the Analyze family, that leaves one or more Analyze protein present in the cancer cells. On the other hand, the normal surrounding cells still have two proteins in the Analyze family. So what happens if we block one Analyze protein in a cancer cell? The cancer cell will have no Analyze proteins left, and this will cause the cell to die. Now let's look at normal cells. These normal cells still have two Analyze proteins, so blocking one Analyze protein will leave one Analyze protein, which means the cell will be fine. This is very theoretical, so the authors wanted to see if it is possible to specifically kill cancer cells by blocking or removing another member of the Analyze family. And this is actually exactly what they found. The cancer cells that had accidentally deleted a member of the Analyze family, along with the tumor suppressors, died after treatment with an Analyze inhibitor. Whereas the normal cells did not. Instead, the normal cells kept on dividing, as if nothing had ever happened. In addition, the Analyze inhibitor prevented the cancer cells from making tumors when injected into mice. This treatment method is surprisingly very specific, definitely much more specific than our current mainstream chemotherapy treatments for these types of cancers that also kills normal cells. This treatment, on the other hand, only kills cancer cells that contain this particular passenger mutation. So what did this study show? This study showed that passenger mutations can be used to differentiate between a normal and a cancer cell. This is because certain passenger mutations can make a cancer cell more sensitive to a specific drug, in this case an Analyze inhibitor, than a normal cell, even if this passenger mutation does not contribute to causing the cancer. By using these findings, the authors were able to specifically kill cancer cells, and not normal cells. This finding was very surprising for multiple reasons. Number one, it is one of the first studies trying to target the cancer without targeting the tumor suppressor that is driving the cancer growth. Number two, this study provides a very accurate way of targeting specifically the cancer cells. Number three, this study may further the exciting notion of personalized medicine by choosing cancer treatments based on what types of passenger mutations are present in a particular patient tumor. Of course, there is still a lot of work that needs to be done before this study can be translated into promising therapies for cancer patients in the clinic. The system that was used in this study provides basic proof of principle to direct potential therapies in humans, but it is still very artificial. For example, it is possible that in a whole organism, the cancer finds a way to increase the protein levels of the other analyzed proteins to compensate for the loss of one of the members of the family. If the cancer cells do this, the analyzed inhibitor treatment may not be as effective in killing the cancer cells. So next, it will be crucial to test this in a whole organism, such as the mouse, to see how the cancers evolve in a tumor environment. For now, this study provides one of the first pieces of evidence that may be the best way to target cancers that are driven by the deletion of tumor suppressors, is by looking at what passenger mutations have occurred in the deletion event, an attempt to target specifically the cancer cell using this type of collateral damage. As you can see, scientists are always trying to rethink ways to approach our enemy in the war against cancer, and progress is being made every day in the laboratory to understand what is programmed in the DNA of a cancer cell and how we can use this information to stop the cancer in its tracks. This video has been provided to you by Eureka Science. To stay in touch with Eureka Science, like us on Facebook, follow us on Twitter, subscribe to our YouTube channel, or visit us at www.eurekascience.com. Thank you for watching!