Molecular-targeted therapies in the treatment of squamous cell carcinomas of the head and neck

Curr Opin Oncol. 2008 May;20(3):256-63. doi: 10.1097/CCO.0b013e3282f9b575.

Abstract

Purpose of review: 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.

Recent findings: 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.

Summary: 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Angiogenesis Inhibitors / therapeutic use
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / therapeutic use
  • Biomarkers, Tumor / analysis
  • Carcinoma, Squamous Cell / drug therapy*
  • Carcinoma, Squamous Cell / metabolism
  • Carcinoma, Squamous Cell / mortality
  • Cetuximab
  • ErbB Receptors / antagonists & inhibitors*
  • Head and Neck Neoplasms / drug therapy*
  • Head and Neck Neoplasms / metabolism
  • Head and Neck Neoplasms / mortality
  • Humans
  • Neoplasm Recurrence, Local / drug therapy*
  • Neoplasm Recurrence, Local / mortality
  • Phosphatidylinositol 3-Kinases / metabolism
  • Protein Kinases / metabolism
  • Proto-Oncogene Proteins c-akt / metabolism
  • Randomized Controlled Trials as Topic
  • Receptor, IGF Type 1 / drug effects
  • Signal Transduction / drug effects
  • TOR Serine-Threonine Kinases

Substances

  • Angiogenesis Inhibitors
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Antineoplastic Agents
  • Biomarkers, Tumor
  • Protein Kinases
  • Phosphatidylinositol 3-Kinases
  • MTOR protein, human
  • TOR Serine-Threonine Kinases
  • ErbB Receptors
  • Receptor, IGF Type 1
  • Proto-Oncogene Proteins c-akt
  • Cetuximab