Pan-ERBB Inhibitors Synergize With KRAS Inhibitors in Rectal Cancer.

ABSTRACT:

Background

Emerging RAS inhibitors show promise in treating KRAS-mutated malignancies, but resistance mechanisms limit their clinical efficacy. Given recent clinical findings associating KRAS mutations with reduced response to neoadjuvant therapy in rectal cancer (RC), we aimed to investigate their impact on treatment outcomes and explore potential therapeutic strategies.

Methods

We conducted a retrospective analysis of 390 rectal cancer patients to evaluate the association of KRAS mutations with disease-free survival (DFS) and response to therapy. We assessed the efficacy of KRAS inhibitors in rectal cancer cell lines, patient-derived organoids (PDOs), and patient-derived cell lines (PDCLs), and explored adaptive resistance mechanisms through transcriptomic profiling and un

SUBMITTER: Buchloh J 

PROVIDER: S-EPMC12605991 | biostudies-literature | 2025 Nov

REPOSITORIES: biostudies-literature