Preventing Treatment Resistance by Co-Targeting Androgen Receptor and SRC/MEK1-Dependent Epithelial to Mesenchymal Transition

About Preventing Treatment Resistance by Co-Targeting Androgen Receptor and SRC/MEK1-Dependent Epithelial to Mesenchymal Transition

What this means to patients: The successful development of a combination drug treatment strategy (inhibition of AR and EMT) should prevent metastasis and the development of treatment resistance.

Synopsis: Epithelial to mesenchymal transition (EMT) is a process by which cancer cells become migratory and invasive, resulting in cancer metastasis and treatment resistance. Dr. Reiter and colleagues hypothesize that interrupting the adaptive EMT response induced by treatment resistance will prolong disease free survival. The research team proposes a randomized Phase II, three-armed neoadjuvant (treatment prior to prostatectomy) clinical study comparing the inhibition of two upstream mediators of EMT with maximal androgen blockade in a population of high-risk patients. Data from the clinical trial and preclinical models will help to identify alternative drivers of EMT, new targets and new combinations to optimally inhibit metastasis.

Rob Reiter, MD

University of California, Los Angeles

Co-investigators:

Hong Wu, MD, PhD; Owen Witte, MD; Jiaoti Huang, MD, PhD; Matthew Rettig, MD; Steve Horvath, PhD, University of California, Los Angeles