Mutation-driven vulnerabilities in Small Cell Lung Cancer
Small Cell Lung Cancer (SCLC) is one of the deadliest types of cancer, with a 5-year survival of less than 5%. In the absence of targeted therapies, chemotherapy with Cisplatin and Etoposide remains the backbone of the current first line and the recent addition of immunotherapy improves the median survival by only two months.
The aims of our research are 1: the identification of molecular and phenotypic differences between cancerous cells and healthy cells and 2: the investigation of how these differences can be exploited to generate a therapeutic window. In particular, we strive to obtain a comprehensive overview of the phenotype of SCLC using genetic tools such as whole-genome CRISPR-Cas9 screens and PiggyBac screens, mutation and expression data from patients and the large amount of biological information available in databases such as The Cancer Genome Atlas (TCGA) and the Genotype-Tissue Expression (GTEx) project. We then test the efficacy of compounds targeting SCLC-specific traits using solid preclinical models, such as autochthonous mice and organoid cultures, which allow us to simulate the first line and the second line settings, with the overall goal of improving the standard of care for Small Cell Lung Cancer.