Identification of a novel ATM inhibitor with cancer cell specific radiosensitization activity.

ABSTRACT: Treatment of advanced head and neck squamous cell carcinoma (HNSCC) is plagued by low survival and high recurrence rates, despite multimodal therapies. Presently, cisplatin or cetuximab is used in combination with radiotherapy which has resulted in minor survival benefits but increased severe toxicities relative to RT alone. This underscores the urgent need for improved tumor-specific radiosensitizers for better control with lower toxicities. In a small molecule screen targeting kinases, performed on three HNSCC cell lines, we identified GSK635416A as a novel radiosensitizer. The extent of radiosensitization by GSK635416A outperformed the radiosensitization observed with cisplatin and cetuximab in our models, while exhibiting virtually no cytotoxicity in the absence of radiation and in nor

SUBMITTER: Dohmen AJC 

PROVIDER: S-EPMC5650312 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature