Cell Type-specific Adaptive Signaling Responses to KRAS^G12C Inhibition.

ABSTRACT:

Purpose

Covalent inhibitors of KRAS^G12C specifically target tumors driven by this form of mutant KRAS, yet early studies show that bypass signaling drives adaptive resistance. Although several combination strategies have been shown to improve efficacy of KRAS^G12C inhibitors (KRASi), underlying mechanisms and predictive strategies for patient enrichment are less clear.

Experimental design

We performed mass spectrometry-based phosphoproteomics analysis in KRAS^G12C cell lines after short-term treatment with ARS-1620. To understand signaling diversity and cell type-specific markers, we compared proteome and phosphoproteomes of KRAS^G12C cells. Gene expression patterns of KRAS^G12C cell lines and lung tumor tissues were examine

SUBMITTER: Solanki HS 

PROVIDER: S-EPMC9940280 | biostudies-literature | 2021 May

REPOSITORIES: biostudies-literature