RT Journal Article
T1 Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation
A1 Simon, Iris
A1 Perales, Sonia
A1 Casado-Medina, Laura
A1 Rodríguez-Martínez, Alba
A1 Garrido-Navas, Maria del Carmen
A1 Puche-Sanz, Ignacio
A1 Diaz-Mochon, Juan J.
A1 Alaminos, Clara
A1 Lupiañez, Pablo
A1 Lorente, Jose A.
A1 Serrano, María J.
A1 Real, Pedro J.
K1 Castration resistant prostate cancer
K1 Androgen receptor
K1 AR-V7
K1 AR-V9
K1 Transcriptional regulation
K1 Novel hormonal agents
K1 Abiraterone
K1 Enzalutamide
K1 Cross-resistance
K1 Neoplasias de la próstata resistentes a la castración
K1 Andrógenos
K1 Elementos reguladores de la transcripción
K1 Acetato de abiraterona
AB 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.
PB MDPI
YR 2021
FD 2021-03-23
LK http://hdl.handle.net/10668/4185
UL http://hdl.handle.net/10668/4185
LA en
NO Simon I, Perales S, Casado-Medina L, Rodríguez-Martínez A, Garrido-Navas MDC, Puche-Sanz I, et al. Cross-Resistance to Abiraterone and Enzalutamide in Castration Resistance Prostate Cancer Cellular Models Is Mediated by AR Transcriptional Reactivation. Cancers. 2021 Mar 23;13(6):1483
DS RISalud
RD Apr 5, 2025