title: Are KRAS/BRAF mutations potent prognostic and/or predictive biomarkers in colorectal cancers?
abstract: KRAS and BRAF mutations lead to the constitutive activation of EGFR signaling through the oncogenic Ras/Raf/Mek/Erk pathway. Currently, KRAS is the only potential biomarker for predicting the efficacy of anti-EGFR monoclonal antibodies (mAb) in colorectal cancer (CRC). However, a recent report suggested that the use of cetuximab was associated with survival benefit among patients with p.G13D-mutated tumors. Furthermore, although the presence of mutated BRAF is one of the most powerful prognostic factors for advanced and recurrent CRC, it remains unknown whether patients with BRAF-mutated tumors experience a survival benefit from treatment with anti-EGFR mAb. Thus, the prognostic or predictive relevance of the KRAS and BRAF genotype in CRC remains controversial despite several investigations. Routine KRAS/BRAF screening of pathological specimens is required to promote the appropriate clinical use of anti-EGFR mAb and to determine malignant phenotypes in CRC. The significance of KRAS/BRAF mutations as predictive or prognostic biomarkers should be taken into consideration when selecting a KRAS/BRAF screening assay. This article will review the spectrum of KRAS/BRAF genotype and the impact of KRAS/BRAF mutations on the clinicopathological features and prognosis of patients with CRC, particularly when differentiating between the mutations at KRAS codons 12 and 13. Furthermore, the predictive role of KRAS/BRAF mutations in treatments with anti-EGFR mAb will be verified, focusing on KRAS p.G13D and BRAF mutations.
authors: Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi Suntogun, Shizuoka 411-8777, Japan. t.yokota@scchr.jp
authors: Tomoya
authors: T
authors: Yokota
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000235:genetics*; D003106:Colon / Q000378:metabolism / Q000473:pathology; D015179:Colorectal Neoplasms / Q000175:diagnosis* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D009154:Mutation; D011379:Prognosis; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D012007:Rectum / Q000378:metabolism / Q000473:pathology; D018631:ras Proteins / Q000235:genetics*
chemical_list: D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins