Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions
Pituitary Gonadotropin-Releasing Hormone receptors (GnRH-R) mediate the activity of the hypothalamic decapeptide GnRH, thus playing a key role in the regulation of the reproductive axis. Early-stage prostate cancer (PCa) is dependent on serum androgen levels, and androgen-deprivation therapy (ADT),...
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MDPI AG
2020-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/24/9511 |
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| author | Fabrizio Fontana Monica Marzagalli Marina Montagnani Marelli Michela Raimondi Roberta M. Moretti Patrizia Limonta |
| author_facet | Fabrizio Fontana Monica Marzagalli Marina Montagnani Marelli Michela Raimondi Roberta M. Moretti Patrizia Limonta |
| author_sort | Fabrizio Fontana |
| collection | DOAJ |
| description | Pituitary Gonadotropin-Releasing Hormone receptors (GnRH-R) mediate the activity of the hypothalamic decapeptide GnRH, thus playing a key role in the regulation of the reproductive axis. Early-stage prostate cancer (PCa) is dependent on serum androgen levels, and androgen-deprivation therapy (ADT), based on GnRH agonists and antagonists, represents the standard therapeutic approach for PCa patients. Unfortunately, the tumor often progresses towards the more aggressive castration-resistant prostate cancer (CRPC) stage. GnRH receptors are also expressed in CRPC tissues, where their binding to both GnRH agonists and antagonists is associated with significant antiproliferative/proapoptotic, antimetastatic and antiangiogenic effects, mediated by the Gαi/cAMP signaling cascade. GnRH agonists and antagonists are now considered as an effective therapeutic strategy for CRPC patients with many clinical trials demonstrating that the combined use of these drugs with standard therapies (i.e., docetaxel, enzalutamide, abiraterone) significantly improves disease-free survival. In this context, GnRH-based bioconjugates (cytotoxic drugs covalently linked to a GnRH-based decapeptide) have been recently developed. The rationale of this treatment is that the GnRH peptide selectively binds to its receptors, delivering the cytotoxic drug to CRPC cells while sparing nontumor cells. Some of these compounds have already entered clinical trials. |
| first_indexed | 2024-03-10T14:04:58Z |
| format | Article |
| id | doaj.art-80ccef83b7344be1ace2a9ca929496cb |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T14:04:58Z |
| publishDate | 2020-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-80ccef83b7344be1ace2a9ca929496cb2023-11-21T00:45:26ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-012124951110.3390/ijms21249511Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological FunctionsFabrizio Fontana0Monica Marzagalli1Marina Montagnani Marelli2Michela Raimondi3Roberta M. Moretti4Patrizia Limonta5Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, ItalyDepartment of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, via Balzaretti 9, 20133 Milan, ItalyPituitary Gonadotropin-Releasing Hormone receptors (GnRH-R) mediate the activity of the hypothalamic decapeptide GnRH, thus playing a key role in the regulation of the reproductive axis. Early-stage prostate cancer (PCa) is dependent on serum androgen levels, and androgen-deprivation therapy (ADT), based on GnRH agonists and antagonists, represents the standard therapeutic approach for PCa patients. Unfortunately, the tumor often progresses towards the more aggressive castration-resistant prostate cancer (CRPC) stage. GnRH receptors are also expressed in CRPC tissues, where their binding to both GnRH agonists and antagonists is associated with significant antiproliferative/proapoptotic, antimetastatic and antiangiogenic effects, mediated by the Gαi/cAMP signaling cascade. GnRH agonists and antagonists are now considered as an effective therapeutic strategy for CRPC patients with many clinical trials demonstrating that the combined use of these drugs with standard therapies (i.e., docetaxel, enzalutamide, abiraterone) significantly improves disease-free survival. In this context, GnRH-based bioconjugates (cytotoxic drugs covalently linked to a GnRH-based decapeptide) have been recently developed. The rationale of this treatment is that the GnRH peptide selectively binds to its receptors, delivering the cytotoxic drug to CRPC cells while sparing nontumor cells. Some of these compounds have already entered clinical trials.https://www.mdpi.com/1422-0067/21/24/9511castration-resistant prostate cancer (CRPC)GnRH receptors (GnRH-R)antiproliferative/proapoptotic activityGnRH agonistsGnRH antagonistscytotoxic GnRH-based bioconjugates |
| spellingShingle | Fabrizio Fontana Monica Marzagalli Marina Montagnani Marelli Michela Raimondi Roberta M. Moretti Patrizia Limonta Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions International Journal of Molecular Sciences castration-resistant prostate cancer (CRPC) GnRH receptors (GnRH-R) antiproliferative/proapoptotic activity GnRH agonists GnRH antagonists cytotoxic GnRH-based bioconjugates |
| title | Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions |
| title_full | Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions |
| title_fullStr | Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions |
| title_full_unstemmed | Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions |
| title_short | Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions |
| title_sort | gonadotropin releasing hormone receptors in prostate cancer molecular aspects and biological functions |
| topic | castration-resistant prostate cancer (CRPC) GnRH receptors (GnRH-R) antiproliferative/proapoptotic activity GnRH agonists GnRH antagonists cytotoxic GnRH-based bioconjugates |
| url | https://www.mdpi.com/1422-0067/21/24/9511 |
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