Impact of Phosphatidylinositol 3-Kinase and B-Raf Mutations in Rat Sarcoma Wild-Type Metastatic Colorectal Cancer.

Authors

Wenjiang Wang, Tao Wang, Linfeng Qian, Yong Nie

Published in

Journal of visualized experiments : JoVE. Issue 236. Oct 16, 2026. Epub Oct 16, 2026.

Abstract

Activating mutations in phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) and B-Raf proto-oncogene (BRAF) are hypothesized to confer primary resistance to anti-epidermal growth factor receptor (anti-EGFR) monoclonal antibodies in metastatic colorectal cancer (mCRC). However, the clinical impact of these mutations in patients with rat sarcoma (RAS) wild-type tumors remains incompletely characterized. This systematic review and meta-analysis evaluated the association of PIK3CA and BRAF mutations with clinical outcomes in RAS wild-type mCRC patients receiving first-line EGFR inhibitor therapy. A systematic literature search was conducted across PubMed, Embase, the Cochrane Library, Google Scholar, and OVID from inception through June 2019, following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. From 600 screened records, 10 studies comprising 1,478 patients with RAS wild-type mCRC were included. Pooled hazard ratios (HRs) for progression-free survival (PFS) and overall survival (OS), and risk differences (RDs) for objective response rate (ORR), were calculated using fixed- or random-effects models with 95% confidence intervals (CIs). PIK3CA mutations were associated with significantly worse PFS (HR, 1.38; 95% CI, 1.11-1.71; p = 0.004) and OS (HR, 1.58; 95% CI, 1.22-2.05; p < 0.001). BRAF mutations were similarly associated with worse PFS (HR, 1.68; 95% CI, 1.46-1.94; p < 0.001) and OS (HR, 1.27; 95% CI, 1.09-1.49; p = 0.003). No significant difference in ORR was observed for either PIK3CA mutations (RD, -0.12; 95% CI, -0.38 to 0.15; p = 0.38) or BRAF mutations (RD, -0.12; 95% CI, -0.28 to 0.04; p = 0.15) compared with wild-type. These findings confirm that PIK3CA and BRAF mutations are negative prognostic biomarkers in RAS wild-type mCRC, associated with inferior PFS and OS but not ORR. Incorporating BRAF and PIK3CA mutation testing into pretreatment evaluation is supported, and alternative therapeutic strategies for mutation carriers are needed. Prospective validation in larger studies is warranted.

PMID:
42891583
Bibliographic data and abstract were imported from PubMed on 18 Oct 2026.

Read full publication at:
Please sign in to see all details.

Stats

1-terrible, 9-excellent. How would you rate this publication? Sign in in to submit your rating.

Post a comment

You need to be signed in to post comments. You can sign in here.

Comments

There are no comments yet.