Abstract C21: KRAS confers resistance to mechanical compression in pancreatic cancer cells

Physical pressure is fundamentally important for cancer biology, but its effects remain poorly understood. When solid tumors grow confined within surrounding tissue, they build up compressive stress. Given that cells evolved to function in a stable mechanical environment, even slight changes in pressure perturb physiology. Normal cells and early-stage cancer cells stop growing when pressure builds up. In contrast, in advanced cancer, compression can change cellular behavior to drive migration or confer resistance to chemotherapy. This difference implies that cancer cells somehow adapt to physical pressure. Pancreatic ductal adenocarcinoma (PDAC) builds the most compressive stress of any tumor because it grows in the context of a stiff fibrotic microenvironment. We have discovered that KRAS activation, present in u003e90% PDAC, enables survival under pressure. We propose that the prevalence of KRAS mutation in PDAC is partly due to its role in adaption to the compressive microenvironment in pancreatic tumors. Citation Format: Gregory P. Brittingham, Liam J. Holt. KRAS confers resistance to mechanical compression in pancreatic cancer cells [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr C21.