DNA repair protein mutations alter blood cancer sensitivity to cisplatin or gemcitabine in vitro

Chemotherapy is the most widely used cancer treatment, yet patient responses vary greatly. Thus, identification of cancer genomic biomarkers for heightened sensitivity to conventional chemotherapy is a promising strategy to improve patient outcomes. In our study, we used a publicly accessible database, OncoExpress, to investigate whether chemotherapeutic drugs cisplatin (CDDP: platinum-based DNA crosslinker) and gemcitabine (GEM: DNA-synthesis inhibitor) show enhanced or reduced activity against cancer cell lines originating from human blood cancers carrying different types of DNA-repair mutations. A total of 9 DNA-repair protein genes (BRCA1, PAXIP1, WRN1, PARP1, PARP2, NEIL1, MLH1, PMS2, MSH2) were analysed for their sensitivity to cisplatin and gemcitabine using the independent samples t-test and Glass’s delta. We hypothesized that mutations in genes involved in DNA repair could sensitize cancer cells to cytotoxic drugs that induce DNA damage. Our results showed that at a significance level of p<0.10, BRCA1 mutations led to significant sensitization to cisplatin (p=0.057) or gemcitabine (p=0.029). Additionally, WRN (p=0.099) or PARP2 (p=0.045) mutations led to sensitization to gemcitabine.