@misc{10481/67961,
year = {2021},
url = {http://hdl.handle.net/10481/67961},
abstract = {Androgen deprivation therapy (ADT) and novel hormonal agents (NHAs) (Abiraterone
and Enzalutamide) are the goal standard for metastatic prostate cancer (PCa) treatment. Although
ADT is initially effective, a subsequent castration resistance status (CRPC) is commonly developed.
The expression of androgen receptor (AR) alternative splicing isoforms (AR-V7 and AR-V9) has
been associated to CRPC. However, resistance mechanisms to novel NHAs are not yet well understood. Androgen-dependent PCa cell lines were used to generate resistant models to ADT only
or in combination with Abiraterone and/or Enzalutamide (concomitant models). Functional and
genetic analyses were performed for each resistance model by real-time cell monitoring assays,
flow cytometry and RT-qPCR. In androgen-dependent PCa cells, the administration of Abiraterone
and/or Enzalutamide as first-line treatment involved a critical inhibition of AR activity associated
with a significant cell growth inhibition. Genetic analyses on ADT-resistant PCa cell lines showed
that the CRPC phenotype was accompanied by overexpression of AR full-length and AR target
genes, but not necessarily AR-V7 and/or AR-V9 isoforms. These ADT resistant cell lines showed
higher proliferation rates, migration and invasion abilities. Importantly, ADT resistance induced
cross-resistance to Abiraterone and/or Enzalutamide. Similarly, concomitant models possessed an
elevated expression of AR full-length and proliferation rates and acquired cross-resistance to its
alternative NHA as second-line treatment.},
organization = {Instituto de Salud Carlos III

PI17/00989},
organization = {European Regional Development Fund "A way to build Europe"},
organization = {Ramon y Cajal - Ministry of Economy and Competitiveness 

RYC-2015-18382},
organization = {Ministry of Education, Culture and Sport 

FPU14/05461},
organization = {University of Granada},
publisher = {MDPI},
keywords = {Castration resistant prostate cancer},
keywords = {Androgen receptor},
keywords = {AR-V7},
keywords = {AR-V9},
keywords = {Transcriptional regulation},
keywords = {Novel hormonal agents},
keywords = {Abiraterone},
keywords = {Enzalutamide},
keywords = {Cross-resistance},
title = {Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation},
doi = {10.3390/cancers13061483},
author = {Simon, Iris and Perales Romero, Sonia and Casado Medina, Laura and Rodríguez Martínez, Alba and Garrido Navas, María del Carmen and Puche Sanz, Ignacio and Díaz Mochón, Juan José and Lorente Acosta, José Antonio and Lupiañez, Pablo and Serrano, María José and Real, Pedro J.},
}