Autocrine IGF1 signaling mediates pancreatic tumor cell dormancy in the absence of oncogenic drivers

Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. While tumor growth and homeostasis is largely dependent on these oncogenes, a few residual cancer cells are able to survive the ablation of mutant KRAS and c-MYC. By performing a genome-wide gene expression analysis of in vivo-derived bulk tumor cells and residual cancer cells lacking the expression of mutant KRAS or c-MYC, we have identified an increase in autocrine IGF1/AKT signaling as a common survival mechanism in dormant cancer cells. The pharmacological inhibition of IGF-1R reduced residual disease burden and cancer recurrence, suggesting this molecular pathway is crucial for the survival of cancer cells in the absence of the primary oncogenic drivers. Total RNA was extracted from flash-frozen pancreatic cancer tissues before or after doxycycline treatment of tumor transplanted athymic nude mice using the RNeasy Mini Kit (Qiagen).