ATR inhibition sensitizes HPV^- and HPV⁺ head and neck squamous cell carcinoma to cisplatin.

ABSTRACT:

Objectives

Cisplatin is commonly used in the treatment of head and neck squamous cell carcinoma (HNSCC), and the repair of cisplatin-induced DNA damage involves activation of the DNA damage response protein ataxia telangiectasia and Rad3-related (ATR). Resistance to cisplatin therapy exacerbates adverse toxicities and is associated with poor outcomes. Since repair of cisplatin-induced DNA damage contributes to resistance, we hypothesized that inhibition of ATR using AZD6738, a well-tolerated and orally-bioavailable inhibitor, would enhance the sensitivity of HNSCC cells and tumors to cisplatin.

Materials and methods

A panel of human papilloma virus-negative (HPV^-) and HPV⁺ HNSCC cell lines were treated with cisplatin in the absence or presence of AZD673

SUBMITTER: Leonard BC 

PROVIDER: S-EPMC6827881 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature