Abstract
Fibrolamellar Carcinoma (FLC) is a rare and deadly cancer that arises in young, otherwise healthy patients. For patients that cannot be treated with surgery, only 30%-45% survive to 5 years with current treatment options. These poor survival odds highlight the need for new therapeutic targets. Using patient samples, we identified that abnormal function of cyclin-dependent kinase 7 (CDK7) is a key component of pathways that are essential for FLC cancer cell identity and survival. Consequently, drug inhibitors of CDK7 suppressed these abnormal pathways and also caused cancer cell death in a dose-dependent manner. This held true in several patient-derived models of FLC. We then found that inhibition of CDK7 can combine with other drug candidates to increase the therapeutic response in FLC cells. Taken together, this suggests CDK7 is a promising target for future treatment in human FLC.