Novel DNA targeted therapies for head and neck cancers: clinical potential and biomarkers

// Mary Glorieux 1 , Rüveyda Dok 1 and Sandra Nuyts 1, 2 1 KU Leuven, University of Leuven, Department of Oncology, Laboratory of Experimental Radiotherapy, 3000 Leuven, Belgium 2 Department of Radiation Oncology, Leuven Cancer Institute, UZ Leuven, 3000 Leuven, Belgium Correspondence to: Sandra Nuyts, email: sandra.nuyts@uzleuven.be Keywords: HNSCC, DNA targeted agents, radiation sensitization, biomarkers Received: June 13, 2017 Accepted: August 27, 2017 Published: September 16, 2017 ABSTRACT Head and neck squamous cell carcinoma is the sixth most common cancer worldwide and despite advances in treatment over the last years, there is still a relapse rate of 50%. New therapeutic agents are awaited to increase the survival of patients. DNA repair targeted agents in combination with standard DNA damaging therapies are a recent evolution in cancer treatment. These agents focus on the DNA damage repair pathways in cancer cells, which are often involved in therapeutic resistance. Interesting targets to overcome these cancer defense mechanisms are: PARP, DNA-PK, PI3K, ATM, ATR, CHK1/2, and WEE1 inhibitors. The application of DNA targeted agents in head and neck squamous cell cancer showed promising preclinical results which are translated to multiple ongoing clinical trials, although no FDA approval has emerged yet. Biomarkers are necessary to select the patients that can benefit the most from this treatment, although adequate biomarkers are limited and validation is needed to predict therapeutic response.