Autocrine IGF1 Signaling Mediates Pancreatic Tumor Cell Dormancy in the Absence of Oncogenic Drivers

• Main Authors: Nirakar Rajbhandari, Wan-chi Lin, Barbara L. Wehde, Aleata A. Triplett, Kay-Uwe Wagner
• Format: Article
• Language: English
• Published: Elsevier 2017-02-01
• Series: Cell Reports
• Online Access: http://www.sciencedirect.com/science/article/pii/S221112471730178X

Summary: Mutant KRAS and c-MYC are oncogenic drivers and rational therapeutic targets for the treatment of pancreatic cancer. Although tumor growth and homeostasis are 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 reduces residual disease burden and cancer recurrence, suggesting that this molecular pathway is crucial for the survival of cancer cells in the absence of the primary oncogenic drivers. : Rajbhandari et al. demonstrate that an increase in autocrine IGF1 signaling mediates the survival of residual pancreatic cancer cells following the ablation of oncogenic drivers (mutant KRAS and c-MYC). They provide experimental evidence that inhibiting IGF-1R can eradicate minimal residual disease and reduce cancer recurrence in vivo. Keywords: pancreatic cancer, oncogenes, KRAS, c-MYC, cancer dormancy, mouse models, genetic engineering, IGF1 signaling, AKT