The National Cancer Institute (NCI) awarded a 5-year, $384,227 Project Grant (CFDA 93.395 - Cancer Treatment Research) to the Medical University of South Carolina (MUSC) to develop novel therapies for treating non-small cell lung cancer (NSCLC) by targeting the SET oncoprotein. The research aims to define the mechanism by which the drug FTY720 and its mimetics induce necroptosis in NSCLC cells through the generation of ceramidosomes, and to determine the therapeutic potential of targeting SET to suppress NSCLC tumor growth. Additionally, the University of Texas Health Science Center at San Antonio received a sub-award to conduct structural studies on the FTY720-SET-PP2A complex and the ceramidosome using X-ray crystallography and cryo-EM. This project seeks to advance first-in-class treatment options and precision therapy for patients with refractory NSCLC.