Medical Scientist-Programm 2020

Thema: "Investigating tumor biological role of acyl-coA synthetase long chain 5 (ACSL5) in nonsmall cell lung cancer (NSCLC): relevance for tumorigenesis, diagnosis and therapeutics"

Zusammenfassung:
Aberrant genetic alteration of metabolic enzymes or oncogene activation reprogramming the lipid metabolism through regulation of ACSL metabolites is one of remarkable features of cancer. ACSL isoenzymes have different effects on driver mutant NSCLC. ACSL3 and ACSL4 play an oncogenic role in the maintenance of mutant lung cancer, however, little is known about the function of the mitochondrial ACSL5. Our preliminary data showed that ACSL5 is dominantly expressed in EGFR mutant cell lines and it had a potential diagnostic value in lung adenocarcinoma. Therefore a functional relation between EFGR mutations and ACSL5 expression in NSCLC is suggested. In the proposed project, we aim to define the tumor biological role of ACSL5 in NSCLC as well as its relation to EGFR mutation during early tumor development and progression in vitro. In addition, the effect of ACSLs inhibitor in combination with targeted therapy/chemotherapy drugs will be determined by using 3D patient derived tumor organoid. Moreover, the clinical relevance between ACSL5 expression, methylation status and driver mutations will be evaluated and correlated with the clinicopathological findings in vivo. This study will add knowledge on a potential diagnostic and therapeutic value of ACSL5 in human NSCLC.