Treating Genetic Differences in Small Cell Lung Cancer
Small cell lung cancer (SCLC) is the most aggressive subtype of lung cancer . Based on the long-standing belief that SCLC is a uniform disease, treatment is not currently influenced by genetic testing or patient stratification using molecular biomarkers. However, we recently discovered that SCLC is comprised of unique subsets driven by genes called MYC and MYCL, which have distinct features. Building on our discovery of a novel treatment for MYC-driven SCLC, we will use human cells and mouse models to identify therapies that will specifically target MYCL-driven SCLC. This work is expected to contribute to molecular testing of SCLC patients and to ultimately identify more effective treatment options for this deadly cancer.
Update: This year, we determined that these SCLC subtypes also harbor unique sensitivities to DNA damage and cell death, called apoptosis. Each SCLC subset has different expression levels of the anti-apoptotic protein BCL2, as well as different sensitivity to drugs that block BCL2. Our data suggest that BCL2 and other cell death proteins may represent novel drug targets for subtypes of SCLC.