Overview of Current Treatment Options and Investigational Targeted Therapies for Locally Advanced Squamous Cell Carcinoma of the Head and Neck

Matthew Zibelman, Ranee Mehra

Research output: Contribution to journalReview articlepeer-review

27 Scopus citations

Abstract

Patients with squamous cell carcinoma of the head and neck (SCCHN) typically present with locally advanced (LA) stage III or IV disease and are treated with combined-modality therapy with chemotherapy, radiotherapy, and surgery (if resectable). These aggressive, upfront treatment measures are often associated with substantial morbidity, and about half the patients develop locoregional or distant recurrences. Thus, new therapeutic strategies are needed that offer similar efficacy benefits with less toxicity. Current research is focused on selectively targeting signaling pathways involved in the proliferation and malignant transformation of SCCHN cells and the tumor microenvironment. For example, the ErbB receptor pathway has been implicated in the development and progression of SCCHN, and several agents targeting this pathway and downstream effectors are in various phases of clinical investigation. Cetuximab, a monoclonal antibody against epidermal growth factor receptor (EGFR), is the only currently approved targeted therapy for the treatment of LA SCCHN. Additional agents targeting EGFR and other ErbB family members, including monoclonal antibodies (eg, panitumumab, nimotuzumab) and small-molecule tyrosine kinase inhibitors (eg, erlotinib, afatinib, lapatinib) are being studied in LA SCCHN with varying results. Other treatment strategies for LA SCCHN include targeting downstream effectors of signaling and resistance mechanisms to EGFR inhibitors (eg, mammalian target of rapamycin, Src family, and Aurora kinase family). Data from ongoing and future clinical trials will continue to refine current treatment paradigms for LA SCCHN and provide new therapeutic options and potential predictive biomarkers to improve patient efficacy and safety and abrogate resistance.

Original languageEnglish
Pages (from-to)396-406
Number of pages11
JournalAmerican Journal of Clinical Oncology: Cancer Clinical Trials
Volume39
Issue number4
DOIs
StatePublished - Aug 1 2016

Keywords

  • Afatinib
  • Antibodies, Monoclonal, Humanized/therapeutic use
  • Antibodies, Monoclonal/therapeutic use
  • Azepines/therapeutic use
  • Carcinoma, Squamous Cell/therapy
  • Cetuximab/therapeutic use
  • Dasatinib/therapeutic use
  • ErbB Receptors/antagonists & inhibitors
  • Erlotinib Hydrochloride/therapeutic use
  • Head and Neck Neoplasms/therapy
  • Humans
  • Lapatinib
  • Molecular Targeted Therapy
  • Panitumumab
  • Protein Kinase Inhibitors/therapeutic use
  • Pyrimidines/therapeutic use
  • Quinazolines/therapeutic use
  • Quinazolinones/therapeutic use
  • Signal Transduction/drug effects
  • Sirolimus/analogs & derivatives

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