Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck.
OBJECTIVE
The present study reviews recent developments of molecular-targeted therapies in the treatment of recurrent and/or metastatic head and neck squamous cell carcinoma. It also highlights ongoing research regarding predictive markers of sensitivity or resistance to anti-epidermal growth factor receptor agents and discusses some promising novel targets in head and neck squamous cell carcinoma, as well as clinical trial design challenges.


RESULTS
Phase III randomized studies have brought the proof that cetuximab, an anti-epidermal growth factor receptor agent, is able to improve survival, either in combination with radiation therapy or in first-line treatment for recurrent and/or metastatic head and neck squamous cell carcinoma. In addition, promising results have been obtained with antiangiogenic therapies in phase II trials. Some clinical and molecular markers of resistance to anti-epidermal growth factor receptor agents have been identified, but they have not yet been validated for clinical practice. Other interesting targets, such as insulin-like growth factor 1R or the PI3K/AKT/mTOR pathway, have been shown in vitro to play key roles in head and neck squamous cell carcinoma, and their inhibition warrants further evaluations.


CONCLUSIONS
Proof of the concept that molecular-targeted therapy is a valid therapeutic approach for head and neck squamous cell carcinoma has emerged with anti-epidermal growth factor receptor agents. Nevertheless, identification of predictive biomarkers of resistance or sensitivity to these therapies remains the main challenge in the optimal selection of patients most likely to benefit from them.
Le Tourneau
Christophe
C
Department of Medical Oncology, Princess Margaret Hospital, Toronto, Canada.
Siu
Lillian L
LL
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use; D000911:Antibodies, Monoclonal / Q000627:therapeutic use*; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D014408:Biomarkers, Tumor / Q000032:analysis; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D000068818:Cetuximab; D066246:ErbB Receptors / Q000037:antagonists & inhibitors*; D006258:Head and Neck Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000401:mortality; D006801:Humans; D009364:Neoplasm Recurrence, Local / Q000188:drug therapy* / Q000401:mortality; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D011494:Protein Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D016032:Randomized Controlled Trials as Topic; D017526:Receptor, IGF Type 1 / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D058570:TOR Serine-Threonine Kinases
D020533:Angiogenesis Inhibitors; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D000970:Antineoplastic Agents; D014408:Biomarkers, Tumor; D000068818:Cetuximab; D066246:ErbB Receptors; D019869:Phosphatidylinositol 3-Kinases; D011494:Protein Kinases; D051057:Proto-Oncogene Proteins c-akt; D017526:Receptor, IGF Type 1; D058570:TOR Serine-Threonine Kinases; C546842:MTOR protein, human