Prostate cancer resistance
Aytes’s Lab

At The Aytes Lab we aim at identifying mechanisms of cancer progression and therapy resistance by developing a unique series of genetically-engineered mice (GEM) models, which are a key resource for the research lines currently undergoing in my group at IDIBELL. 

A strong research focus since the inception of my group in 2016 has been to understand how changes in the transcriptional networks of cancer cells determine the cell identity and impinge on treatment response. To this end, we initially defined the regulatory networks of metastatic and non-metastatic CRPC and identified a set of epigenetic chromatin remodelers, including Nsd2, strongly associated metastatic progression and survival. This study was the groundwork upon which we build an extensive program to identify epigenetic targets and vulnerabilities to be translated to preclinical stages. 

In parallel, our group has a strong interest in identifying resistance mechanisms to standard of care treatments in prostate cancer, mainly antiandrogens. Mutations in the Androgen Receptor (AR) are known to affect the molecular structure and are the most frequent alteration in prostate cancer. Yet, the structure-function relationship and how disease associated mutations affect the AR function in cancer is unclear. We have recently characterized some of these AR mutations and showed how they define the response to antiandrogenic treatmetns. 

At the crossroads of targeted therapies and conventional chemotherapy lies the use of PARP inhibitors. We are trying to understand the genomic determinants of response to PARP inhibition to expand the therapeutic landscape beyond DNA damage repair deficiency. This is particularly relevant for prostate cancer to expand PARP inhibitors beyond classical synthetic lethality involving HR mutant carriers.

The above-mentioned fundamental and translational research endeavors have been instrumental in consolidating the interdisciplinary Prostate Cancer research Group at IDIBELL, Hospital de Bellvitge (HUB), the Catalan Institute of Oncology (ICO) and University of Barcelona (UB).