RT info:eu-repo/semantics/article
T1 Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment.
A1 Morales González, Manuel José
A1 Martín-Vasallo, Pablo
A1 Ávila, Julio
A2 Medicina InternaDermatología y Psiquiatría
K1 enzalutamide
K1 mineralocorticoid receptor
K1 androgen receptor
K1 androgen receptor inhibitors
K1 glucocorticoid receptor
K1 toxic myocarditis
K1 prostate cancer
K1 aldosterone
K1 spironolactone
AB Enzalutamide is a nonsteroidal inhibitor of the androgen receptor (AR) signaling pathwayand is used to treat patients with metastatic castration-resistant prostate cancer. However, the riskof cardiovascular-related hospitalization in patients with no contraindications for the use of enzalutamide is about 1–2%. To date, the underlying molecular basis of this has not been established. Theandrogen receptor, glucocorticoid receptor (GR) and mineralocorticoid receptor (MR) are nuclear receptors that share structural similarities and have closely related DNA-binding sites and coregulators.In non-epithelial cells, a fine balance of the activities of these receptors is essential to ensure correctcellular function. In this study, we present a molecular characterization of these nuclear receptorsin a prostate cancer patient who developed congestive heart failure after enzalutamide treatment.White cell RNAseq revealed a homozygous rs5522 MR polymorphism and both the rs143711342 andrs56149945 GR polymorphisms, carried in different alleles. No different specific splice isoforms weredetected. Recent research suggests that AR inhibition by enzalutamide makes available a coregulatorthat specifically interacts with the rs5522-mutated MR, increasing its activity and producing adverseeffects on cardiovascular health. We suggest an evaluation of the MR rs5522 polymorphism beforestarting therapy with AR inhibitors.
YR 2022
FD 2022
LK http://riull.ull.es/xmlui/handle/915/40044
UL http://riull.ull.es/xmlui/handle/915/40044
LA en
DS Repositorio institucional de la Universidad de La Laguna
RD 14-abr-2025