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

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. Overall design: 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).