Combined KRAS Inhibition and Immune Therapy Generates Durable Complete Responses in an Autochthonous PDAC Model

Cancer Discov. 2025 Jan 13;15(1):162-178. doi: 10.1158/2159-8290.CD-24-0489.

Abstract

Clinically available KRAS* inhibitors and IO agents alleviated the immunosuppressive tumor microenvironment in PDAC. Profound tumor regression and prolonged survival in an autochthonous PDAC model provide a compelling rationale for combining KRAS* inhibition with IO agents targeting multiple arms of the immunity cycle to combat PDAC.

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal* / drug therapy
  • Carcinoma, Pancreatic Ductal* / genetics
  • Carcinoma, Pancreatic Ductal* / immunology
  • Carcinoma, Pancreatic Ductal* / pathology
  • Carcinoma, Pancreatic Ductal* / therapy
  • Disease Models, Animal
  • Humans
  • Immunotherapy* / methods
  • Mice
  • Pancreatic Neoplasms* / drug therapy
  • Pancreatic Neoplasms* / genetics
  • Pancreatic Neoplasms* / immunology
  • Pancreatic Neoplasms* / pathology
  • Pancreatic Neoplasms* / therapy
  • Proto-Oncogene Proteins p21(ras)* / antagonists & inhibitors
  • Proto-Oncogene Proteins p21(ras)* / genetics
  • Tumor Microenvironment / drug effects

Substances

  • Proto-Oncogene Proteins p21(ras)
  • KRAS protein, human