Tissue factor overexpression promotes resistance to KRAS-G12C inhibition in non-small cell lung cancer.

ABSTRACT: The recently approved KRAS^G12C mutation-specific inhibitors sotorasib and adagrasib (KRAS^G12C-I) represent a promising therapy for KRAS^G12C-driven non-small cell lung cancer (NSCLC). However, many eligible patients do not benefit due to intrinsic or acquired drug resistance. Tissue factor (TF) is overexpressed in KRAS-mutated (KRASmut) NSCLC and is the target of the FDA-approved ADC Tivdak. Here, we employed HuSC1-39, the parent antibody of a clinical stage TF-ADC (NCT04843709), to investigate the role of TF in KRASmut NSCLC. We found that patients with TF-overexpression had poor survival, elevated P-ERK/P-AKT activity levels and low immune effector cell infiltration in the tumor. In a panel of KRAS^G12C cell lines, KRAS^G12C-I response

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC10890931 | biostudies-literature | 2024 Feb

REPOSITORIES: biostudies-literature