Abstract SY36-01: Mechanisms of autophagy addiction in cancer

Abstract

Abstract Autophagy is a catabolic pathway utilized by cells to eat themselves and recycle cellular components to support metabolism and survival in response to starvation. Autophagy also functions to clear damaged proteins and organelles. Autophagy can thereby maintain tissue health and suppress tissue degeneration and cancer initiation in liver, and in this context autophagy is a tumor suppressor. Autophagy, however, is also a survival pathway used by both normal cells and established cancers to sustain metabolism and tolerate stress, and in this context autophagy is a tumor promoter. Activation of a powerful oncogene such as Ras, for example, up-regulates basal autophagy required for tumor cell survival in stress and in tumorigenesis. In Ras-driven cancer cells, defective autophagy causes accumulation of abnormal mitochondria, reduces oxygen consumption, and impairs metabolism causing energy depletion. Thus, without autophagy, tumor cells have impaired stress tolerance that reduces tumorigenesis. As cancers with Ras mutations have a poor prognosis, this “autophagy addiction” suggests that targeting autophagy is valuable new approaches to treat these aggressive cancers. Recent findings demonstrating roles for autophagy in genetically engineered mouse models for cancer and the regulation of nutrient sensing and autophagy regulation by mTOR will be presented. New developments in the approach to and effectiveness of autophagy modulation in cancer therapy and the mechanism of cancer cell death induction will be discussed. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr SY36-01. doi:1538-7445.AM2012-SY36-01