Activating PIK3CA mutations and hedgehog signaling may confer resistance to KRAS inhibition in colorectal cancer (AACR 2024) - Mar 6, 2024 - Abstract #1250; Pres time: Apr 7, 2024; 03:20 PM - 03:35 PM; Location: Room 5 - Upper Level - Convention Center; "KRASG12C mutant CRC cell lines SW837 and SW1463 were treated with Sotorasib (KRASG12C inhibitor), Vismodegib and Taladegib (Hedgehog inhibitors), and cell viability was measured up to 96 hours after treatment. In the AACR Project-GENIE CRC (N = 9441) cohort, KRASG12C tumors (2.6%, 245/9441) were significantly co-mutated with PIK3CAmut (19.2%, 47/245; Odds ratio = 1.7 (95% CI: 1.2 - 2.4), Chi-Square test, p-value = 0.002). Resistance in CRC to KRASG12C inhibitors may be attributed to activated PIK3CA mutations and the Hedgehog signaling pathway. The future study will focus on detailed investigations involving comprehensive transcriptome and exome profiles in tumors and PDX models treated with anti-KRAS drugs in monotherapy and combination therapy."
Colorectal Cancer • Gastrointestinal Cancer • Lung Cancer • Oncology • Solid Tumor • KRAS • PIK3CA
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S. Chowdhury 1; J. Ahmed 2; V. Haridas 1; D. S. Hong 1; S. Kopetz 1; J. Shen1
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