Use Of Dna Repair Proteins Translated From Biomarker Screening To Predict Overall Survival In Patients With Esophageal Cancer Treated With Oxaliplatin Chemotherapy

e13587 Background: Oxaliplatin is first-line chemotherapy for colorectal, gastric, and esophageal cancers. Aim was to identify key determinants of oxaliplatin sensitivity and optimise these biomarkers to select patients for chemotherapy. Methods: High-throughput screening of oxaliplatin sensitivity was performed in a Schizosaccharomyces pombe deletion library of 229 DNA repair strains and Chinese Hamster Ovary (CHO) cell lines with mutations in specific proteins. Biopsies were taken from 50 patients with esophageal cancer, who then received two cycles of oxaliplatin and fluorouracil chemotherapy prior to surgery. Levels of DNA repair proteins were quantified by immunohistochemistry and by qRT-PCR. Results: Twelve lead biomarkers were identified from the preclinical models. In CHO cells, XPF and ERCC1 mutants were approximately 30 times more sensitive than the WT cells (pu003c0.01). In comparison to WT CHO cells, XPF-deficient cells had prolonged delay in mid-late S-phase after oxaliplatin treatment, and persi...