Events Calendar

USC Physical Sciences in Oncology Seminar

Speaker: DEAN FELSHER M.D., PH.D. , Professor of Medicine-Oncology, Pathology and Molecular Imaging, Department of Medicine, Stanford University

Talk Title: Modeling and Predicting Oncogene Addiction

Abstract: Cancers are largely caused by the activation of oncogenes. We have developed an experimental system to model and predict the therapeutic efficacy of targeted therapy of oncogenes. Using the Tet system, we can conditionally regulate oncogene expression in vivo in a temporally controlled and tissue specific manner. We have shown that many oncogenes (MYC, RAS, BCR-ABL) induce tumorigenesis that is completely reversible upon their inactivation. We have described this phenomena as oncogene addiction. Oncogene addiction is associated with proliferative arrest, apoptosis, differentiation, cellular senescence and the shutdown of angiogenesis. The specific consequences of oncogene inactivation depend both on the genetic and cellular context. In some cases, even brief inactivation of an oncogene can result in sustained tumor regression. In other cases, oncogene inactivation is associated with tumor dormancy. Tumor cell intrinsic and host-dependent cell autonomous mechanisms are involved. Tumor cell intrinsic mechanisms appear to involve mechanisms that are dependent upon DNA repair processes, the regulation of protein synthesis and of cellular metabolism. Host-dependent mechanisms include the regulation of angiogenesis and immune cell elimination. In addition, tumor cells secrete autocrine factors critical to oncogene addiction. We have uncovered that oncogene addiction is not cell autonomous and requires an intact host immune system. Specifically, CD4+ T-cells are required for MYC or BCR-ABL inactivation to induce sustained tumor regression. We have found that in the absence of an immune system, oncogene inactivation failed to both induce cellular senescence in tumor cells as well as to shut down angiogenesis in the host. Finally, our experimental model system can be used to model Oncogene Addiction. We have shown that we can use simple mathematical model to predict the therapeutic consequences of oncogene inactivation.

Biography: USC was selected to establish a $16 million cancer research center as part of a new strategy against the disease by the U.S. National Institutes of Health and its National Cancer Institute. The new center is one of 12 in the nation to receive the designation. During the five-year initiative, the Physical Sciences-Oncology Centers will take new, nontraditional approaches to cancer research by studying the physical laws and principles of cancer; evolution and the evolutionary theory of cancer; information coding, decoding, transfer and translation in cancer; and ways to de-convolute cancer's complexity. As part of the outreach component of this grant, the Center for Applied Molecular Medicine is hosting a monthly seminar series.

Host: USC Physical Sciences in Oncology Center

Location: Clinical Science Center (CSC) - #250

Audiences: Everyone Is Invited

Contact: Kristina Gerber