#IDIBELLconnect: Dissecting mechanisms of therapy resistance in lethal prostate cancer

Alvaro Aytés
Resistance and Progression Mechanisms in Prostate Cancer Group

Androgen deprivation therapy (ADT) through bilateral orchiectomy or gonadotropin releasing hormone agonists alone or in combination with antiandrogen is generally the initial treatment for metastatic prostate cancer. Despite initial response rates as high as 90%, nearly all men eventually develop progressive disease, referred as castration resistant prostate cancer (CRPC). Several agents, such as enzalutamide, abiraterone acetate, radium223, docetaxel, and cabazitaxel have demonstrated improvement in overall survival in this clinical situation. However, to this date, no treatments for CRPC are curative. Several mechanisms account for prostate cancer therapy resistance, including mutations in the AR itself, restoration of signaling downstream of the pharmacological blocking and activation of alternative oncogenic pathways. In addition, lineage plasticity and transdifferentiation towards a cellular state that no longer depends on the therapeutic target is an increasingly recognized mechanism of resistance to molecularly targeted cancer therapy. Our group exploits preclinical models to unravel the molecular mechanisms associated to the acquisition of therapy resistance to identify emerging vulnerabilities and new therapeutic opportunities.

Alvaro graduated from the School of Biological Sciences at the University of Barcelona in 2001, and obtained a Master’s degree in Biology and Cellular Pathology at the School of Medicine at the University of Barcelona in 2003. While preparing for his Master’s, he worked as a lab technician first and then as a research assistant at two private laboratories, namely Histopat laboratories S.L and Biopatologia Molecular, Grup Assitencia for two years. For his doctoral studies, he joined the Catalan Institute of Oncology (ICO). He was awarded a fellowship from the ISCIII (BEFI2003). Long before having completed his PhD, he decided that he would pursue a career in academic research. He sought to complement his graduate training with a postdoctoral training abroad at Columbia University, NY, USA. He obtained the Marie Curie—International Outgoing Fellowships (IOF). That was for two years and he spent 7 years as a postdoctoral researcher, authored 9 publications including first authorships in Cell, Cancer Cell, PNAS, Nature Communications, and Cell Reports. In the 2015 call, he was awarded the Miguel Servet and Ramón y Cajal awards from the ISCIII and the MINECO, respectively. He decided to accept the Miguel Servet Award and joined the faculty at IDIBELL as tenure track group leader. Since joining IDIBELL, he has continued receiving funds from the ISCIII while also securing grants from the European Association of Urology, the US Department of Defense, and the BBVA Foundation.