{"entity":{"id":"paper-pik3ca-colorectal-acta-oncol-2014","kind":"paper","name":"The predictive value of KRAS, NRAS, BRAF, PIK3CA and PTEN for anti-EGFR treatment in metastatic colorectal cancer: A systematic review and meta-analysis","aka":[],"tldr":"Review on PIK3CA in Colorectal cancer, in Acta oncologica (2014), one of the most cited Europe PMC records with PIK3CA in its title.","summary":"Background: In metastatic colorectal cancer, mutation testing for KRAS exon 2 is widely implemented to select patients with wild-type tumors for treatment with the monocloncal anti-EGFR antibodies cetuximab and panitumumab. The added predictive value of additional biomarkers in the RAS-RAF-MAPK and PI3K-AKT-mTOR pathways in colorectal cancer is uncertain, which led us to systematically review the impact of alterations in KRAS (outside of exon 2), NRAS, BRAF, PIK3CA and PTEN in relation to the clinical benefit from anti-EGFR treatment.\n\nMethods: In total, 22 studies that include 2395 patients formed the basis for a meta-analysis on alterations in KRAS exons 3 and 4, NRAS, BRAF, and PIK3CA and PTEN and outcome of anti-EGFR treatment. Odds ratios for objective response rate (ORR) and hazard ratios (HR) for progression-free survival (PFS) and overall survival (OS) were calculated.\n\nResults: Mutations in KRAS exons 3 and 4, BRAF, PIK3CA and non-functional PTEN (mutations or loss of protein expression) significantly predicted poor ORR (OR = 0.26, OR = 0.29, OR = 0.39, and OR = 0.41, respectively). Significantly shorter PFS applied to mutations in KRAS exons 3 and 4 (HR = 2.19), NRAS (HR = 2.30) and BRAF (HR = 2.95) and non-functional PTEN (HR = 1.88). Significantly shorter OS applied to mutations in KRAS exons 3 and 4 (HR = 1.78), NRAS (HR = 1.85), BRAF (HR = 2.52), PIK3CA (HR = 1.43) and alterations in PTEN (HR = 2.09).\n\nConclusions: Meta-analysis suggests that mutations in KRAS exons 3 and 4, NRAS, BRAF and PIK3CA and non-functional PTEN predict resistance to anti-EGFR therapies and demonstrates that biomarker analysis beyond KRAS exon 2 should be implemented for prediction of clinical benefit from anti-EGFR antibodies in metastatic colorectal cancer.\n\nIndexed on Europe PMC as PubMed record 24666267 (DOI 10.3109/0284186x.2014.895036). Its title names PIK3CA and its text names Colorectal cancer; PubMed types it as a review (Meta-Analysis, Systematic Review). It was matched automatically to the idea \"Get biomarker-directed aspirin after colorectal surgery into labels and guidelines\" and no figure has been checked by an editor.","asOf":"2026-09-22","links":[{"label":"Acta Oncol 2014","url":"https://doi.org/10.3109/0284186x.2014.895036"},{"label":"PubMed","url":"https://pubmed.ncbi.nlm.nih.gov/24666267/"},{"label":"Europe PMC","url":"https://europepmc.org/article/MED/24666267"}],"tags":["europepmc-ingest"],"related":[],"cancers":[],"sections":[],"technologies":[],"targets":[],"drugs":[],"companies":[],"institutions":[],"pathways":[],"terms":[],"trials":[],"people":[],"bottlenecks":[],"keyPapers":[],"journals":["acta-oncologica"],"dependsOn":[],"notes":[],"journal":"Acta oncologica","year":2014,"doi":"10.3109/0284186x.2014.895036","pmid":"24666267","authors":"Therkildsen C, Bergmann TK, Henrichsen-Schnack T, et al.","paperType":"meta-analysis","findings":[],"whatItMeans":"One of the most cited reviews Europe PMC returns for PIK3CA in Colorectal cancer, so it is a natural first reading for anyone weighing the idea it is linked from. The record was linked automatically by title and abstract; read the abstract above and the paper itself before relying on any figure.","caveats":["Matched by PIK3CA in the title and Colorectal cancer in the title or abstract of the Europe PMC record; the summary reproduces the record's abstract and no figure has been verified against the full paper.","A review summarises other studies; the primary reports it cites are the evidence."]},"route":"/key-papers/paper-pik3ca-colorectal-acta-oncol-2014/","neighbours":{"journal":[{"id":"acta-oncologica","kind":"journal","name":"Acta oncologica","route":"/journals/acta-oncologica/"}],"idea":[{"id":"idea-reg-aspirin-pik3ca-implementation","kind":"idea","name":"Get biomarker-directed aspirin after colorectal surgery into labels and guidelines","route":"/ideas/idea-reg-aspirin-pik3ca-implementation/"}]}}