 My name is Dean Felscher. I'm a professor at Stanford University, and I'm glad to talk to you briefly about a paper I wrote for Anka Target called BIM mediates oncogene inactivation induced apoptosis in multiple transgenic mouse models of acute lymphoplastic leukemia. My laboratory has spent the last 16 years studying mechanisms of oncogene addiction. Oncogene addiction is a phenomena whereby cancers can exhibit almost a miraculous regression upon the inactivation of a single driver oncogene. In particular, we've studied how cancers can be addicted to the myconcogene. Myc is one of the most commonly activated oncogenes in human cancer. Previously, we've shown that when you engineer cancers that are driven by the myconcogene, that turning off the myconcogene can lead to a remarkable regression of these tumors associated with a dramatic induction of apoptosis. But until very recently and until this specific publication published in Anka Target, we had not described the exact mechanism. The work I'm now outlining for you was performed under leadership of a senior postdoctoral fellow in my lab, Yulin Li, with the help of another fellow, Anja Deutschman. He also had help from a former graduate student, Peter Choi, and a former fellow in my lab, Alice Phen. In this work, we found that in a variety of oncogene-driven models of acute lymphobastic leukemia, that shutting down the oncogene that drove these cancers led to apoptosis caused by a specific apoptotic regulatory protein, BIM. Now BIM has been well known and characterized to be a major regulation of apoptosis, but only until very recently has it been suggested to play a role in therapeutic apoptosis. Previous reports have suggested that some targeted therapies may work through the BIM oncogene, and this suggested to us the possibility that this may be a more central regulator how oncogenes maintain survival and regulate the absence of apoptotic programs. What we found is in a variety of different models when you turn off MIC or ABL or the RAS oncogenes and tumors undergo apoptosis, this is causally dependent on the BIM apoptotic regulator. Now what's important about these results are several things. First of all, they suggest that there may be a common mechanism of oncogene addiction associated apoptosis, and that BIM is one of the central regulators of this process. So this provides a novel mechanistic insight. But second of all, and perhaps more importantly, they suggest that therapies that target oncogenes, in particular for the treatment of leukemia and lymphoma, that their efficacy will depend on the ability to induce the safe apoptotic program, and thus we've identified a biological marker of successful therapeutic action. But finally, they may suggest new ways of thinking about therapeutic development. So targeting this program and being able to restore this apoptotic program may be a very effective treatment for particular types of cancer. Now this work focused on the study of models of leukemia and lymphoma, but we think these results are likely to extend to other types of cancer as well. Thus, we found in my laboratory evidence that solid tumors caused by driver oncogenes such as MIC also will undergo apoptosis when you turn off the MIC oncogene. We recognize, however, that the mechanisms could be more nuanced, that BIM may not be the only key apoptotic regulator, that different kinds of tumors may utilize different apoptotic programs, and that the magnitude of the activity may depend very much on specific type of tumor. Current efforts in the laboratory are to attempt to identify the precise mechanisms by which these apoptotic mechanisms regulated, and we're conducting screens for therapeutics that may be able to mimic the effects of turning off these oncogenes and restore these apoptotic programs. I'm excited to continue this work that has led to a very productive and exciting insight into the biology and pathogenesis of these cancers.