Genetic mechanisms of cisplatin resistance in ovarian cancer cell lines

Cancer remains as one of the most common causes of mortality worldwide accounting for 9.6 million deaths globally of which ovarian cancer is third highest ranked gynecological cancer. Standard treatment of ovarian cancer remains to be cytoreductive surgery and use of platinum-based drugs such as cisplatin. Cisplatin cytotoxic action is through formation of DNA adducts. Although they are effective as first line of treatment for ovarian cancers, patients suffer recurrence and develop drug resistance. Mechanisms behind cisplatin resistance in ovarian cancer are not well elucidated, however they are known to be multifactorial. This project utilizes cancer cell lines adapted to cisplatin as a model of acquired resistance to cisplatin. Three ovarian cancer cell lines Colo704, EF021 and EF027, parental and cisplatin-adapted, were investigated to identify possible mechanisms of resistance. The study involved analysis of exome sequencing data to differentiate the variants present in each cell line. A comparison was made between the parental and resistant cell lines and between the acquired variants of each resistant cell line to find common mechanisms that may account for resistance emergence. Affected genes belonged to several pathways that were found to be over-represented and/or enriched, in particular the extracellular matrix pathway, ion gated channels, mismatch repair and nucleotide excision repair, and signaling pathways. The study gave an insight on pathways and genes that are prospective future drug targets.