Clinical Instructor
Department of Medicine

Project Title:  Targeting ferroptosis in resistant melanoma

Tomas Ganz, PhD, MD – UCLA

Multidisciplinary Expertise:
Iron metabolism, cancer metabolism, animal models, bioinformatics, clinical hematology/oncology

Project Description:
New treatments are required for patients with metastatic melanoma that have progressed after MAPK pathway inhibition and immune therapies.  Melanoma can evade these therapies through dedifferentiation.  This process, which resembles epithelial-to-mesenchymal transition in carcinomas, is characterized by transcriptional reprogramming.  Bioinformatic interrogation of a melanoma dedifferentiation signature in a large publicly-available pharmacogenomics database led to the discovery of a subtype-specific susceptibility to ferroptosis-inducing agents.  This project aims to validate this computational lead, establish the in vivo efficacy of ferroptosis drugs, and study the mechanistic basis of ferroptosis in dedifferentiated melanomas.