Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment
Enzalutamide is a nonsteroidal inhibitor of the androgen receptor (AR) signaling pathway and is used to treat patients with metastatic castration-resistant prostate cancer. However, the risk of cardiovascular-related hospitalization in patients with no contraindications for the use of enzalutamide i...
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MDPI AG
2022-05-01
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| Online Access: | https://www.mdpi.com/2227-9059/10/6/1271 |
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| author | Manuel Morales Pablo Martín-Vasallo Julio Ávila |
| author_facet | Manuel Morales Pablo Martín-Vasallo Julio Ávila |
| author_sort | Manuel Morales |
| collection | DOAJ |
| description | Enzalutamide is a nonsteroidal inhibitor of the androgen receptor (AR) signaling pathway and is used to treat patients with metastatic castration-resistant prostate cancer. However, the risk of 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. The androgen 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 correct cellular function. In this study, we present a molecular characterization of these nuclear receptors in 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 and rs56149945 GR polymorphisms, carried in different alleles. No different specific splice isoforms were detected. Recent research suggests that AR inhibition by enzalutamide makes available a coregulator that specifically interacts with the rs5522-mutated MR, increasing its activity and producing adverse effects on cardiovascular health. We suggest an evaluation of the MR rs5522 polymorphism before starting therapy with AR inhibitors. |
| first_indexed | 2024-03-10T00:22:23Z |
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| institution | Directory Open Access Journal |
| issn | 2227-9059 |
| language | English |
| last_indexed | 2024-03-10T00:22:23Z |
| publishDate | 2022-05-01 |
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| series | Biomedicines |
| spelling | doaj.art-fe53d0cd481a4c4289711b08d221cdc02023-11-23T15:41:54ZengMDPI AGBiomedicines2227-90592022-05-01106127110.3390/biomedicines10061271Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide TreatmentManuel Morales0Pablo Martín-Vasallo1Julio Ávila2Service of Medical Oncology, University Hospital Nuestra Señora de Candelaria, 38010 Santa Cruz de Tenerife, SpainLaboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, 38200 La Laguna, SpainLaboratorio de Biología del Desarrollo, UD de Bioquímica y Biología Molecular and Centro de Investigaciones Biomédicas de Canarias (CIBICAN), Universidad de La Laguna, 38200 La Laguna, SpainEnzalutamide is a nonsteroidal inhibitor of the androgen receptor (AR) signaling pathway and is used to treat patients with metastatic castration-resistant prostate cancer. However, the risk of 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. The androgen 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 correct cellular function. In this study, we present a molecular characterization of these nuclear receptors in 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 and rs56149945 GR polymorphisms, carried in different alleles. No different specific splice isoforms were detected. Recent research suggests that AR inhibition by enzalutamide makes available a coregulator that specifically interacts with the rs5522-mutated MR, increasing its activity and producing adverse effects on cardiovascular health. We suggest an evaluation of the MR rs5522 polymorphism before starting therapy with AR inhibitors.https://www.mdpi.com/2227-9059/10/6/1271enzalutamidemineralocorticoid receptorandrogen receptorandrogen receptor inhibitorsglucocorticoid receptortoxic myocarditis |
| spellingShingle | Manuel Morales Pablo Martín-Vasallo Julio Ávila Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment Biomedicines enzalutamide mineralocorticoid receptor androgen receptor androgen receptor inhibitors glucocorticoid receptor toxic myocarditis |
| title | Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment |
| title_full | Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment |
| title_fullStr | Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment |
| title_full_unstemmed | Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment |
| title_short | Genetic Profiling of Glucocorticoid (NR3C1) and Mineralocorticoid (NR3C2) Receptor Polymorphisms before Starting Therapy with Androgen Receptor Inhibitors: A Study of a Patient Who Developed Toxic Myocarditis after Enzalutamide Treatment |
| title_sort | genetic profiling of glucocorticoid nr3c1 and mineralocorticoid nr3c2 receptor polymorphisms before starting therapy with androgen receptor inhibitors a study of a patient who developed toxic myocarditis after enzalutamide treatment |
| topic | enzalutamide mineralocorticoid receptor androgen receptor androgen receptor inhibitors glucocorticoid receptor toxic myocarditis |
| url | https://www.mdpi.com/2227-9059/10/6/1271 |
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