Biomarkers for predicting the efficacy of anti-epidermal growth factor receptor antibody in the treatment of colorectal cancer.
Anti-epidermal growth factor receptor (EGFR) antibodies have been widely utilized as a standard treatment for metastatic colorectal cancer (CRC). Anti-EGFR antibodies bind competitively to EGFRs to inhibit receptor activation and subsequent signal transduction of the RAS/RAF/MEK pathway and PI3K/AKT pathway. By inhibiting EGFR-mediated signal transduction, anti-EGFR antibodies inhibit cell growth, invasion, metastasis and angiogenesis, and they induce apoptosis. The IgG1-type antibody cetuximab is also capable of inducing antibody-dependent cellular cytotoxicity. Several studies have shown that KRAS mutation is a useful biomarker for predicting the efficacy of anti-EGFR agents, and the major guidelines for the treatment of CRC recommend the use of anti-EGFR antibody only for the cancers with wild-type KRAS. Alterations of other genes, including BRAF, NRAS, PTEN and AKT, and EGFR expression/gene copy number have also been reported to be candidate biomarkers for predicting the efficacy of anti-EGFR agents. The predictive values of these biomarkers are still controversial and further investigations are required.
Department of Gastroenterology and Oncology, Institutes of Health Biosciences, University of Tokushima Graduate School, Tokushima, Japan.
Yasuyuki
Y
Okada
Hiroshi
H
Miyamoto
Takahiro
T
Goji
Tetsuji
T
Takayama
D061067:Antibodies, Monoclonal, Humanized / Q000008:administration & dosage / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D014408:Biomarkers, Tumor / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000276:immunology; D005544:Forecasting; D006801:Humans; D009154:Mutation
D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D066246:ErbB Receptors