Adaptive KRAS-MAPK signaling mediates resistance to CD73 blockade in pancreatic ductal adenocarcinoma (AACRPanCa 2026) - Oct 15, 2026 - Abstract #B070; "LsL-KrasG12D; LsL-Trp53R172H/+; Pdx:Cre (KPC) syngeneic flank tumors were treated with vehicle, Quemliclustat, daraxonrasib, trametinib, daraxonrasib plus Quemliclustat, or trametinib plus Quemliclustat. Adaptive KRAS-MAPK signaling represents a previously unrecognized resistance mechanism that emerges following CD73 inhibition and sustains the CD73-adenosine immunosuppressive program in PDAC. Dual targeting of KRAS and CD73 suppresses adaptive signaling, reduces stromal remodeling, and produces superior antitumor activity, providing a mechanistically informed therapeutic strategy to overcome resistance to CD73-directed therapy in pancreatic cancer.Citation Format:Khadija Turabi, Shwetapadma Dash, Lincoln Strickland, Alyssa Waller, MacKenzie Demmel, Jennifer M. Bailey-Lundberg. Adaptive KRAS-MAPK signaling mediates resistance to CD73 blockade in pancreatic ductal adenocarcinoma [abstract]."
Oncology • Pancreatic Cancer • Pancreatic Ductal Adenocarcinoma • Solid Tumor • ADORA2B • CD73 • ENTPD1 • KRAS • NT5E
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Khadija Turabi; Shwetapadma Dash; Lincoln Strickland; Alyssa Waller; MacKenzie Demmel; Jennifer M. Bailey-Lundberg
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