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Are KRAS/BRAF Mutations Potent Prognostic and/or Predictive Biomarkers in Colorectal Cancers?

[ Vol. 12 , Issue. 2 ]

Author(s):

Tomoya Yokota   Pages 163 - 171 ( 9 )

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.

Keywords:

Anti-EGFR monoclonal antibody, BRAF, Cetuximab, Chemotherapy, Clinicopathological features, Colorectal cancer, KRAS codon 12, EGFR, Prognostic biomarker

Affiliation:

Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi Suntogun,Shizuoka 411-8777, Japan.



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