Abstract 3493: Comprehensive analysis of the DNA repair enzyme signature in tumor and blood cells from head and neck cancer patients and correlation with clinical data from a 18-months follow-up study

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is the sixth leading cancer worldwide. It is often associated with a history of smoking/alcohol consumption or exposure to the human papilloma virus (HPV). Beyond surgery, treatment usually includes DNA damaging treatments i.e. cisplatin/5FU combined or not with radiation therapy. Treatment failure rates are still high due to intrinsic and acquired mechanisms of resistance, largely involving DNA repair mechanisms. Here we precisely examined the main DNA repair mechanisms susceptible to drive tumor progression and resistance to treatment, using a miniaturized comprehensive functional approach on biochip. Enzymatic DNA repair profiles were compared for lymphocytes and tumor biopsies taken before treatment from 38 patients in a prospective clinical study. We simultaneously investigated double strand break repair pathways (HR, NHEJ, SSA, alt-EJ), excision/synthesis repair mechanisms (BER, NER, ICLR) and several glycosylases/AP endonuclease activities, using lysates prepared from the samples. Results were correlated with physiologic and lifestyle/risk factors, TNM tumor classification, treatment-induced adverse effects, and disease progression or death at 18 months. Analysis of blood cells and biopsies provided different and complementary information. Indeed, the prediction of treatment-induced severe toxicity was effective on blood cells. Several risk factors significantly affected specific repair activities of tumor cells. HPV positive and negative tumors displayed distinct DNA repair profiles and, cancer progression and tumor staging correlated with deregulated repair activities in tumors. Interestingly, the most affected DNA repair activities concerned double strand break repair, repair of cisplatin adducts, and repair of oxidative damage. This accurate DNA repair profiling represents an innovative strategy to reveal tumor diversity and better understand the impact of risk factors. It improved our understanding of the role of DNA repair in the development and progression of cancer. In addition, the use of a panel of DNA repair-based enzymatic biomarkers is more accurate than the single parameter approach in stratifying patients into different groups, thus allowing for more effective therapeutic strategies. Citation Format: Sylvie Sauvaigo, Giovanna Muggiolu, Sarah Libert, Bertrand Treillard, Gersende Alphonse, Christian A. Righini, Philippe Ceruse, Pierre Philouze, Claire Rodriguez-Lafrasse. Comprehensive analysis of the DNA repair enzyme signature in tumor and blood cells from head and neck cancer patients and correlation with clinical data from a 18-months follow-up study [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 3493.