Discovery suggests opportunity to improve effectiveness of KRAS inhibitors against pancreatic cancer
Combination therapy that targets both basal‑state and classical‑state cells improves KRAS inhibitor efficacy in pancreatic cancer.
Researchers at Memorial Sloan Kettering discovered a new resistance mechanism to KRAS inhibitors in pancreatic cancer, revealing that basal‑state tumor cells respond strongly to KRAS inhibition whereas classical‑state cells survive and drive relapse. Combining KRAS inhibitors with conventional chemotherapy or targeted agents that eliminate classical cells markedly reduces tumor size (~70 %) and delays relapse in mouse models. These findings suggest that early, combination therapy could improve outcomes in patients with KRAS‑G12D pancreatic cancer.
KRAS inhibitors are a promising but short‑term therapy for KRAS‑driven pancreatic cancer. A new resistance pathway has been identified, and converting resistance to a vulnerability could enable durable responses in patients whose tumors have aggressive basal subtypes.
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