In Situ RAS:RAF Binding Correlates with Response to KRASG12C Inhibitors in KRASG12C-Mutant Non-Small Cell Lung Cancer.

ABSTRACT:

Purpose

Therapeutic efficacy of KRASG12C(OFF) inhibitors (KRASG12Ci) in KRASG12C-mutant non-small cell lung cancer (NSCLC) varies widely. The activation status of RAS signaling in tumors with KRASG12C mutation remains unclear, as its ability to cycle between the active GTP-bound and inactive GDP-bound states may influence downstream pathway activation and therapeutic responses. We hypothesized that the interaction between RAS and its downstream effector RAF in tumors may serve as indicators of RAS activity, rendering NSCLC tumors with a high degree of RAS engagement and downstream effects more responsive to KRASG12Ci compared with tumors with lower RAS-RAF interactions.

Experimental design

We developed a method for measuring in situ RAS binding to RAF in cancer samples using

SUBMITTER: Kato R 

PROVIDER: S-EPMC11924342 | biostudies-literature | 2025 Mar

REPOSITORIES: biostudies-literature