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: Tomoya Yokota
• Journal: Anti-cancer agents in medicinal chemistry (Anticancer Agents Med Chem) Vol. 12 Issue 2 Pg. 163-71 (Feb 2012) ISSN: 1875-5992 [Electronic] Netherlands
• PMID: 22043994 (Publication Type: Journal Article, Review)

Chemical References

• Biomarkers, Tumor
• KRAS protein, human
• Proto-Oncogene Proteins
• BRAF protein, human
• Proto-Oncogene Proteins B-raf
• Proto-Oncogene Proteins p21(ras)
• ras Proteins

Topics

• Animals
• Biomarkers, Tumor (genetics)
• Colon (metabolism, pathology)
• Colorectal Neoplasms (diagnosis, genetics, pathology)
• Humans
• Mutation
• Prognosis
• Proto-Oncogene Proteins (genetics)
• Proto-Oncogene Proteins B-raf (genetics)
• Proto-Oncogene Proteins p21(ras)
• Rectum (metabolism, pathology)
• ras Proteins (genetics)