62IN - Novel agents and paradigms in development in HNSCC

Date 01 October 2012
Event ESMO Congress 2012
Session Biologically based treatment in head and neck squamous cell carcinoma
Topics Anti-Cancer Agents & Biologic Therapy
Head and Neck Cancers
Presenter Antonio Jimeno
Authors A. Jimeno
  • University of Colorado School of Medicine, 80045 - Aurora/US

Abstract

HNSCC is a particularly challenging disease due to the rarity of activating oncogene mutations and prevalence of mutations in tumor suppressor genes such as P53 and NOTCH1 with 47% and 19% mutation rates, respectively. The epidermal growth factor receptor (EGFR) inhibitor cetuximab is the only targeted drug for HNSCC, but to date, and despite its relatively low clinical efficacy, there are no validated patient selection strategies. HPV types 16 and 18 through integration and replication of the E6/E7 proteins are the etiologic cause of an increasing percentage of HNSCC, which is becoming an epidemic among younger patients in Western countries. There is growing evidence that HPV+ and HPV- HNSCC have a different biology, and we can expect it will require different therapy. In addition to embellishments to anti-EGFR therapy new areas of research in HNSCC include PI3K inhibition (with the role of genetic selection still to be determined), novel anti-angiogenesis and anti-lymphangiogenesis such as ALK1 modulators, multikinase inhibitors, multi-targeted monoclonal antibodies aimed at more efficiently abrogating EGFR signaling and co-activated pathways, and agents aiming at inhibiting the HNSCC stem cell compartment such as Hedgehog pathway inhibitors.

Disclosure

A. Jimeno: Research laboratory funding: - Infinity - Oncothyreon - Onconova Patent ownership: - Oncothyreon - Onconova