Key Findings:
- RAS mutations negatively predicted reduced therapeutic response in CRC, with consensus molecular subtype 3 (CMS3) independently associated with non-response.
- Responders and non-responders differed in gene expression and pathway activity, with MYC/E2F targets and MTORC1 signaling enriched in non-responders.
- A 26-gene predictive model for therapeutic response in RAS-mutant CRC showed strong performance in external validation, supporting its clinical use in guiding therapy.