Research Projects

The study aims to fill the knowledge gap in understanding the functional role of fatty acid synthase (FASN) in recalcitrant squamous cell lung cancer (SCLC). Although a recent study found that FASN mutations associated with better survival in chemotherapy-treated SCLC patients, the functional role of FASN in recalcitrant SCLC remains unknown. The researchers are evaluating FASN-induced effects on drug resistance in SCLC through activation of cancer stem cells (CSCs), and generating structure-guided novel small-molecular FASN inhibitors to test against chemoresistant SCLC in vitro. SCLC is the deadliest subtype of lung cancers, with a 5-year survival rate of less than 5%. Chemotherapy-treated patients often relapse within months with acquired resistance to further treatments, leading to metastasis and cancer-related death. The study identifies fatty acid synthase (FASN) as the top gene associated with better prognosis in chemotherapy-treated SCLC patients, but its functional role in recalcitrant SCLC is not known. FASN has been overexpressed in CSCs, which drive drug resistance and have been shown to enhance proliferation of CSCs. The proposed study aims to analyze the role of FASN in SCLC drug-resistance, develop FASN inhibitors using structure-guided rational inhibitor designing, and evaluate the potential of FASN inhibitors against SCLC chemoresistant properties. This study could revolutionize the current understanding and treatment of drug resistance in SCLC, based on FASN's role in regulating cancer cell metabolism and cancer stem cell activity.