The use of Next generation sequencing (NGS) to decipher the chemotherapy related genes in resistant versus parental breast cancer cells

Breast cancer is considered the most prevalent type of cancer in Omani females with an increased incidence rate. Advanced Breast cancer patients are usually treated with neoadjuvant chemotherapy followed by surgery. Response to treatment varies among patients, some show complete pathological and clinical response however others don?t respond, and finally, they relapse with aggressive disease. In this proposal, we will be studying the different mechanisms of resistance to chemotherapy using total RNA sequencing. Three resistant breast cancer cell lines to three chemotherapeutic drugs were developed previously, Luminal A (MCF7), Luminal B (BT-474), and Triple Negative (MDA-MB-231). The resistant cells to Adriamycin, cyclophosphamide, and paclitaxel will be subjected to transcriptomic analysis to investigate the markers expressed upon resistance to either the combination of Adriamycin and cyclophosphamide or to the three drugs in the different cell lines. Once a gene or set of genes shows differential expression among the different cell lines to the different drugs, it will be edited using the CRISPR case9 system to study its functional role in resistance. The outcome of such analysis will allow us to identify signature genes that can be future precise drug targets for patients who don?t respond to treatment and will show the difference among the different subtypes of breast cancer and finetune the choice of treatment in a more specified and personalized manner.