Is biomarker research advancing in the era of personalized medicine for head and neck cancer?
Recent progress in molecular biology and translational research has initiated an era of personalized medicine in head and neck clinical oncology. The genetic information defined by biomarker analysis in tumors and individuals is indispensable for the administration of molecular targeting agents. The epidermal growth factor receptor (EGFR) signaling pathway is an important therapeutic target in head and neck squamous cell carcinoma (HNSCC). The use of an anti-EGFR monoclonal antibody (mAb), cetuximab (Cmab), has been approved for the treatment of patients with head and neck cancer. Although KRAS mutation has been established as a potential biomarker for predicting the efficacy of anti-EGFR mAb in colorectal cancer, little is known about predictive markers for Cmab in head and neck cancer. Optimal predictive and prognostic markers as well as safety markers are required to promote the appropriate clinical use of Cmab and to determine malignant phenotypes in head and neck cancer. This article first reviews the role of EGFR signaling in HNSCC. The article then focuses on Ras/Raf/Mek/Erk and PTEN/PI3K/Akt signaling pathways as predictive markers for Cmab. Subsequently, the molecular basis and clinical outcome of human papillomavirus (HPV)-positive cancer is highlighted, and the potential role of anti-EGFR target therapy for HPV-positive HNSCC is discussed. Finally, the possible mechanism for resistance to anti-EGFR target therapy is reviewed, and I discuss approaches to overcome the resistance with reference to an ongoing clinical trial.
Division of Gastrointestinal Oncology, Shizuoka Cancer Center, 1007 Shimonagakubo Nagaizumi Sunto-gun, Shizuoka, 411-8777, Japan, t.yokota@scchr.jp.
Tomoya
T
Yokota
D061067:Antibodies, Monoclonal, Humanized / Q000009:adverse effects / Q000627:therapeutic use; D014408:Biomarkers, Tumor; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000502:physiology; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D058990:Molecular Targeted Therapy; D009154:Mutation; D051059:PTEN Phosphohydrolase / Q000502:physiology; D027383:Papillomaviridae / Q000302:isolation & purification; D019869:Phosphatidylinositol 3-Kinases / Q000502:physiology; D057285:Precision Medicine; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000502:physiology; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000502:physiology; D012871:Skin Diseases / Q000139:chemically induced; D000077195:Squamous Cell Carcinoma of Head and Neck; D018631:ras Proteins / Q000235:genetics
D061067:Antibodies, Monoclonal, Humanized; D014408:Biomarkers, Tumor; C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C494929:PTEN protein, human; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins; D000068818:Cetuximab