Functional genomic screening to identify novel approaches to overcome drug resistance in Small Cell Lung Cancer

Small cell lung cancer is an aggressive and highly metastatic disease that represents around 15% of all lung cancer patients. The majority of patients (70%) present in the clinic with advanced disease that has spread beyond the lung. The treatment options available to these patients are limited to platinum-based chemotherapy. This is effective in the majority of patients, however almost all will rapidly relapse with platinum resistant disease. There is no effective second line therapies which has meant these patients have an appalling overall survival rate of 2-5% which has not improved over the past three decades. Therefore there is an urgent and unmet need to understand the mechanisms of platinum resistance and how to overcome it to provide meaningful improvements in patient outcomes. My laboratory has developed panels of platinum resistant small cell lung cancer cell lines and genetically engineered mouse models. In this project we will use CRISPR/Cas9 technology to perform unbiased pooled screening (whole genome or draggable targets) to identify mechanisms of resistance which will be interrogated in vitro and in vivo.