Genetic variation and response to platinum chemotherapy in cancer treatment: a review article

Platinum-based chemotherapies, including cisplatin, carboplatin, and oxaliplatin, are foundational treatments of multiple solid tumor types, inducing cell death via DNA cross-linking. Genetic markers of DNA repair have been extensively studied as determinants of response. We searched MEDLINE (2000-2026) and appraised 204 publications, contributing 212 study entries, against a four-tier evidence hierarchy, distinguishing throughout between prognostic vs. predictive biomarker claims. Defects in nucleotide excision repair and homologous recombination repair are associated with outcomes with platinum therapy across nearly every tumor type examined. Evidence supporting these markers as predictors of platinum-specific benefit is far narrower. Of 212 entries reviewed, only 10 compared platinum against an alternative regimen under randomized allocation, and five of these found no differential benefit. Homologous recombination deficiency predicts benefit from platinum-based therapy in high-grade serous ovarian carcinoma and randomized data support a predictive role for germline BRCA1/2 mutations in triple-negative breast cancer. For ERCC1, two randomized trials disagree, and no assay identified in this review distinguishes the single isoform competent to form the incision complex with XPF.