Abstract B59: Autophagy mediates senescence and supports survival upon treatment with anti-mitotic drugs

Abstracts: AACR Special Conference: Metabolism and Cancer; June 7-10, 2015; Bellevue, WA Anti-mitotic drugs such as paclitaxel and vinblastine have been used as front-line therapies for the treatment of many cancers. These agents induce activation of a spindle assembly checkpoint (SAC), which leads to a prolonged mitotic arrest that culminates in cell death. However, this anti-proliferative mechanism is often impeded by the development of chemo-resistance. A major cause of resistance is mitotic slippage. Mitotic slippage is a process whereby cells exit mitosis and undergo an abnormal cytokinesis failure despite an active SAC. Till now the mechanisms leading to mitotic slippage and post slippage survival are not fully understood. Here we find that cancer cells “slip”, form multinucleated cells and undergo senescence upon treatment with anti-mitotic drugs. Our data indicate that autophagy plays an important role in senescence induction. Inhibition of autophagy via pharmacological drugs or silencing of autophagy-associated genes could over-ride senescence. This promotes DNA damage accumulation, which attenuates long term survival upon anti-mitotic drug treatment. Taken together, our data suggest that autophagy mediated-senescence contributes to chemo-resistance and could serve as a potential combinatorial target with anti-mitotic drugs in future clinical trials. Note: Guo Ke has been added to the author list. The online version of this abstract differs from the original print proceedings. Citation Format: Cheng Bing, Guo Ke, Alex Wong, Karen Crasta. Autophagy mediates senescence and supports survival upon treatment with anti-mitotic drugs. [abstract]. In: Proceedings of the AACR Special Conference: Metabolism and Cancer; Jun 7-10, 2015; Bellevue, WA. Philadelphia (PA): AACR; Mol Cancer Res 2016;14(1_Suppl):Abstract nr B59.