A Cell-Based Method for Identification of Chemotherapy Resistance Cancer Genes

Here we describe a method for identifying genes and genetic pathways responsible for chemoresistance in cancer cells. The method is based on generation and characterization of matched pairs of chemotherapy-sensitive/chemotherapy-resistant cancer cell lines. In this protocol we are using endometrial cancer cell lines treated with carboplatin and paclitaxel, which are first-line chemotherapies for gynecologic malignancies. The chemoresistant cells and their chemosensitive counterparts are used for downstream applications including bulk RNA-sequencing analysis to identify a set of genes and pathways that are associated with chemoresistance. Identification of pathways responsible for innate or acquired chemoresistance is of paramount importance for the identification of biomarkers for cancer risk stratification and prognosis, and as a pharmacogenomics model for identification of alternative chemotherapy approaches for treatment of patients with recurrent and chemoresistant disease.