63IN - Implications for clinical practice and trial design

Date 01 October 2012
Event ESMO Congress 2012
Session Biologically based treatment in head and neck squamous cell carcinoma
Topics Cytotoxic agents
Head and Neck Cancers
Biological therapy
Presenter Amanda Psyrri
Authors A. Psyrri
  • Internal Medicine, Attikon University Hospital, 12462 - Athens/GR


Targeted strategies have been developed in head and neck squamous cancer (HNSCC) in order to increase effectiveness and decrease toxicity. Epidermal growth factor receptor (EGFR) inhibitors are firmly established in HNSCC but the critical issue has been patient selection. Other recently developed novel pathway inhibitors hold significant promise and are being tested in phase 1, 2 and 3 trials either alone or concomitantly with radiotherapy or chemoradiotherapy. One such class of agents, the poly(ADP-ribose) polymerase (PARP) inhibitors, has shown activity in conjunction with radiotherapy in head and neck cancer cell lines. Pre-clinical data suggest that PARP inhibitors may potentiate the effects of radiotherapy in head and neck cancer cell lines and xenograft models. Sonic hedgehog (Shh) pathway plays an important role in HNSCC progression and should be considered a potential therapeutic target. One clinical arena where targeted therapies may also find place is in the adjuvant or prevention setting where minimal disease or precancerous lesions can be affected by shutdown of a single or few targets. Future directions lie in understanding the molecular basis of the mechanism of action of the drugs currently undergoing clinical evaluation. Increased understanding of the cell signaling processes involved might aid patient selection. Advances in genomics are revolutionizing the discovery of biomarkers and should improve the tumor selectivity of novel agents. There is also a need for the development of methods that can be used in pharmacodynamic studies in humans. A better understanding of the signaling pathways will not only inform our knowledge of cancer development but also help to refine the classification as well as the treatment of the disease.


The author has declared no conflicts of interest.