Selecting the best targeted agent in first-line treatment of unresectable liver metastases from colorectal cancer: does the bench have the answers?
For physicians facing patients with organ-limited metastases from colorectal cancer, tumor shrinkage and sterilization of micrometastatic disease is the main goal, giving the opportunity for secondary surgical resection. At the same time, for the majority of patients who will not achieve a sufficient tumor response, disease control remains the predominant objective. Since FOLFOX or FOLFIRI have similar efficacies, the challenge is to define which could be the most effective targeted agent (anti-EGFR or anti-VEGF) to reach these goals. Therefore, a priori molecular identification of patients that could benefit from anti-EGFR or anti-VEGF monoclonal antibodies (i.e. the currently approved targeted therapies for metastatic colorectal cancer) is of critical importance. In this setting, the KRAS mutation status was the first identified predictive marker of response to anti-EGFR therapy. Since it has been demonstrated that tumors with KRAS mutation do not respond to anti-EGFR therapy, KRAS status must be determined prior to treatment. Thus, for KRAS wild-type patients, the choices that remain are either anti-VEGF or anti-EGFR. In this review, we present the most updated data from translational research programs dealing with the identification of biomarkers for response to targeted therapies.
Division of Medical Oncology, USC Norris Comprehensive Cancer Center, Los Angeles, CA 90033, USA. leonorbenhaim@gmail.com
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L
Benhaim
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Loupakis
M J
MJ
Labonte
H J
HJ
Lenz
D000970:Antineoplastic Agents / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000473:pathology*; D066246:ErbB Receptors / Q000037:antagonists & inhibitors; D006801:Humans; D008113:Liver Neoplasms / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics / Q000556:secondary*; D058990:Molecular Targeted Therapy; D011518:Proto-Oncogene Proteins / Q000032:analysis; D016283:Proto-Oncogene Proteins p21(ras); D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors; D018631:ras Proteins / Q000032:analysis
D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D042461:Vascular Endothelial Growth Factor A; D066246:ErbB Receptors; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins