Predictive biomarkers of clinical response to targeted antibodies in colorectal cancer.
Targeted mAbs to VEGFR and EGFR are well-established therapies for the treatment of colorectal cancer. The costs and toxicities associated with these novel treatments are not insignificant, and therefore molecular markers that predict treatment efficacy are needed to individualize the therapy administered to each patient. Recent data in this research field support KRAS mutation testing to guide the selection of EGFR inhibitors for the treatment of colorectal cancer. This review discusses the evidence that KRAS mutation analysis can indicate a beneficial response to EGFR inhibitors, and the potential and limitations of other mutations in the VEGF and EGF signaling pathways as predictive molecular markers in this setting.
Chua
Wei
W
Concord Repatriation General Hospital, Department of Medical Oncology, Sydney Cancer Centre, Hospital Road, New South Wales 2139, Australia.
Moore
Melissa M
MM
Charles
Kellie A
KA
Clarke
Stephen J
SJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000906:Antibodies / Q000627:therapeutic use*; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D061067:Antibodies, Monoclonal, Humanized; D000068258:Bevacizumab; D015415:Biomarkers / Q000378:metabolism*; D002986:Clinical Trials as Topic; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000276:immunology; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000037:antagonists & inhibitors / Q000276:immunology; D006801:Humans; D020935:MAP Kinase Signaling System / Q000502:physiology; D051059:PTEN Phosphohydrolase / Q000235:genetics / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics / Q000378:metabolism; D011110:Polymorphism, Genetic; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D040262:Receptors, Vascular Endothelial Growth Factor / Q000276:immunology; D015398:Signal Transduction / Q000502:physiology; D016896:Treatment Outcome; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D048490:raf Kinases / Q000235:genetics / Q000378:metabolism; D018631:ras Proteins / Q000235:genetics / Q000378:metabolism
D020533:Angiogenesis Inhibitors; D000906:Antibodies; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D015415:Biomarkers; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D000068258:Bevacizumab; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D040262:Receptors, Vascular Endothelial Growth Factor; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D048490:raf Kinases; D051059:PTEN Phosphohydrolase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins