Alterations in targetable molecular pathways are enriched in KRAS wild-type (WT) pancreatic cancer (PC)

Authors:

Philip Agop Philip, Joanne Xiu, Michael J. Hall, Andrew Eugene Hendifar, Emil Lou, Jimmy J. Hwang, Jun Gong, Michelle Ellis, Moh'd M. Khushman, Davendra Sohal, A. Craig Lockhart, Benjamin, Adam Weinberg, John Marshall, Axel Grothey, Anthony Frank Shields, W. Michael Korn

Conclusions:

KRAS WT PC is significantly more enriched with targetable alterations (e.g., BRAF, ALK, ROS1, NRG1, MSI-H) as compared to KRAS MT tumors, suggesting potential benefit of using targeted therapies. – The use of WTS in combination with NGS identifies activated molecular pathways in the majority of KRAS WT tumors. – Based on our findings, comprehensive profiling of PC at the DNA and RNA level is recommended to provide patients with therapeutic opportunities beyond standard treatments. – TMB and MSI tend to be higher in KRAS WT tumors; microenvironment inferred from WTS using MCP counter suggest more activated innate immunity with a lower fibroblast abundance, suggesting unique immune treatment strategy design.

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