Molecular Targeted Therapies in the Management of Head and Neck Squamous Cell Carcinoma: Recent Developments and Perspectives

Alexandre      Bozec; Frederic      Peyrade; Gerard      Milano

doi:10.2174/187152013804910370

Abstract

Current development of molecular targeted therapies in oncology is particularly active. This paper is a review of the recent advances in the field of molecular targeted therapies for head and neck squamous cell carcinoma (HNSCC). We analyze not only the recently published and ongoing clinical trials, but also the relevant preclinical studies, in order to identify the future directions of research in the field of HNSCC.

As epidermal growth factor receptor (EGFR) signaling pathway plays a key role in the growth of HNSCC, EGFR, with its downstream effectors, represents the main target of the new therapeutic agents currently in development. Today, cetuximab, an anti-EGFR monoclonal antibody, is the only targeted therapy approved for the treatment of HNSCC in patients with locally advanced tumors, in association with radiotherapy, and in patients with recurrent or metastatic disease, in association with platinum-based chemotherapy. Future advances are expected with the integration of cetuximab and other anti-EGFR agents into induction chemotherapeutic regimens or in association with concurrent chemoradiotherapy for locally advanced tumors. Besides EGFR inhibition, new molecular targeted therapies such as mTOR, Src kinase, or IGF-1R inhibitors, acting on other activated molecular signaling pathways, are being developed. As these innovative molecules are beginning to be used in clinical practice, the identification of predictive markers for efficacy and toxicity is now a crucial issue.

Keywords: Cetuximab, EGFR, Head and neck squamous cell carcinoma, Molecular targeted therapies, Angiogenesis, oropharyngeal tumors, carboplatin, taxane, cisplatin arm.