Ras mutations are frequent in advanced myeloma (MM) with resistance to resistance to currently available therapies. Erastin is a compound that selectively kills cells that harbor such mutations and our preclinical work with PRLX93936, a compound derived from erastin, shows its potent activity against MM cells both in laboratory cultures and animal studies. In this project, we will identify molecular markers that can help predict which MM patients will respond to PRLX93936 and develop potent and safe combinations of this agent with other anti-MM drugs, with the ultimate goal to help the design of future clinical trials of PRLX93936, or other agents of this class of drugs, for MM treatment.