Abstract IA-007: Exploiting DNA repair defects in head and neck squamous cell carcinoma

Abstract

Abstract DNA damage repair pathways govern genomic integrity and determine cellular sensitivities to radiation and chemotherapeutic agents. Recent genetic studies highlight the identification of an increasing number of DNA repair gene defects in many different cancer types. DNA damage response and repair inhibitors on the other hand provide opportunities to exploit such defects inherent to cancer cells. Combined with radiotherapy they are highly effective radiosensitizers that show some tumor specificity in that they cause greater radiation dose enhancement in cells with repair defects. To optimize such potent combinations, robust and sensitive biomarkers are needed to 1) assess effectivity and guide clinical trial designs and 2) to identify repair defects in individual patients. Radiotherapy is a mainstay in the treatment of advanced HPV-negative head and neck squamous cell carcinoma (HNSCC). There is a need for improved treatment options in this patient population. Indicating particular crosslink repair sensitivity and frequent cancer cell repair defects, cumulative cisplatin dose is an important factor in determining patient outcomes after chemoradiotherapy. Indeed, preclinical and genetic data highlight the frequent manifestation of DNA crosslink repair defects in HNSCC. Genetic biomarkers have therefore been generated and tested to support the identification of patients in need for novel treatment options and of crosslink repair defects in HNSCC for combination with PARP inhibitors. Citation Format: Conchita Vens. Exploiting DNA repair defects in head and neck squamous cell carcinoma [abstract]. In: Proceedings of the AACR Virtual Special Conference on Radiation Science and Medicine; 2021 Mar 2-3. Philadelphia (PA): AACR; Clin Cancer Res 2021;27(8_Suppl):Abstract nr IA-007.