This proposal is to request support for a Keystone Symposia meeting entitled Metabolism and Cancer Progression, organized by Eileen P. White, Craig B. Thompson and Chi Van Dang, which will be held in Vancouver, British Columbia from March 12 - 17, 2010. Otto Warburg initially drew attention to the distinct metabolic state of tumors compared to normal tissues over 75 years ago, where tumor cells commonly favor glycolysis over oxidative phosphorylation even in the presence of oxygen (Warburg effect or aerobic glycolysis). Insight into the role and mechanism of this metabolic switch in tumorigenesis and the utility of, and means to therapeutically exploit, altered metabolism in cancer was not clear other than for utilization for FDGPET imaging. Recently the metabolic requirements of tumor cells and the links to common pathway alterations in human cancers have been gradually emerging. It is now apparent that metabolic demand in tumor cells is high due to deregulation of cell growth, and that this constitutive activation of growth signaling pathways can disconnect cellular metabolism from nutrient and growth factor availability. Subversion of cellular metabolism for biosynthetic purposes is required to sustain deregulated tumor cell growth but can also restrict energy production which, in turn, can limit tumor cell adaptation to metabolic stress. Hypoxic and acidic conditions in the tumor microenvironment are byproducts of these events and are common features of the tumor microenvironment that can activate stress responses, influence tumor growth, and impair treatment. Many of the oncogenic pathways altered in tumor cells modulate cell metabolism while enabling growth in these adverse conditions. Adaptation of tumor cells to stress through activation of the catabolic pathway of autophagy, as well as its role in damage mitigation and promoting tumor cell survival to metabolic stress, is also now emerging. The vision for this meeting is to bring together leaders in the fields of cancer, signaling and metabolism to discuss emerging discoveries and their application to improving cancer therapy. Opportunities for interdisciplinary interactions will be significantly enhanced by the concurrent meeting on Cell Death Pathways: Apoptosis, Autophagy and Necrosis, which will share a keynote address and two plenary sessions with this meeting.
Recent developments linking tumor metabolism to oncogenic mechanisms have provided long-awaited revelations explaining important aspects of tumor biology with direct clinical translation implications. This conference will provide a platform for clinical and translational investigators to link the basic science to disease applications;discussions will to help propel the field of cancer signaling and metabolism forward.