Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer
Abstract
:1. Introduction
2. The Androgen/AR Axis in CRPC
2.1. Intratumoral Synthesis of Androgens
2.2. Androgen Receptor Amplification
2.3. Androgen Receptor Mutations
2.4. Androgen Receptor Splice Variants
2.5. Androgen Receptor: Transcription Factors and Coregulators
3. The GnRH/GnRH-R Axis in CRPC
3.1. Gonadotropin-Releasing Hormone
3.2. Gonadotropin-Releasing Hormone Receptors: Molecular Structure
3.3. Gonadotropin-Releasing Hormone Receptors: Antiproliferative Activity
3.4. Gonadotropin-Releasing Hormone Receptors: Antimetastatic and Antiangiogenic Activity
3.5. Gonadotropin-Releasing Hormone Receptors: Signal Transduction
4. Androgen and Gonadotropin-Releasing Hormone Receptors: Molecular Targets for Therapeutic Strategies in CRPC
5. Conclusions and Future Perspectives
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
- Siegel, R.L.; Miller, K.D.; Fuchs, H.E.; Jemal, A. Cancer Statistics, 2021. CA Cancer J. Clin. 2021, 71, 7–33. [Google Scholar] [CrossRef]
- Labrie, F.; Candas, B.; Gomez, J.L.; Cusan, L. Can combined androgen blockade provide long-term control or possible cure of localized prostate cancer? Urology 2002, 60, 115–119. [Google Scholar] [CrossRef]
- Singer, E.A.; Golijanin, D.J.; Miyamoto, H.; Messing, E.M. Androgen deprivation therapy for prostate cancer. Expert Opin. Pharmacother. 2008, 9, 211–228. [Google Scholar] [CrossRef]
- Litwin, M.S.; Tan, H.J. The Diagnosis and Treatment of Prostate Cancer: A Review. JAMA 2017, 317, 2532–2542. [Google Scholar] [CrossRef]
- Onozawa, M.; Akaza, H.; Hinotsu, S.; Oya, M.; Ogawa, O.; Kitamura, T.; Suzuki, K.; Naito, S.; Namiki, M.; Nishimura, K.; et al. Combined androgen blockade achieved better oncological outcome in androgen deprivation therapy for prostate cancer: Analysis of community-based multi-institutional database across Japan using propensity score matching. Cancer Med. 2018, 7, 4893–4902. [Google Scholar] [CrossRef]
- Tamada, S.; Iguchi, T.; Kato, M.; Asakawa, J.; Kita, K.; Yasuda, S.; Yamasaki, T.; Matsuoka, Y.; Yamaguchi, K.; Matsumura, K.; et al. Time to progression to castration-resistant prostate cancer after commencing combined androgen blockade for advanced hormone-sensitive prostate cancer. Oncotarget 2018, 9, 36966–36974. [Google Scholar] [CrossRef] [Green Version]
- Perner, S.; Cronauer, M.V.; Schrader, A.J.; Klocker, H.; Culig, Z.; Baniahmad, A. Adaptive responses of androgen receptor signaling in castration-resistant prostate cancer. Oncotarget 2015, 6, 35542–35555. [Google Scholar] [CrossRef] [Green Version]
- Galletti, G.; Leach, B.I.; Lam, L.; Tagawa, S.T. Mechanisms of resistance to systemic therapy in metastatic castration-resistant prostate cancer. Cancer Treat. Rev. 2017, 57, 16–27. [Google Scholar] [CrossRef] [PubMed]
- Nemes, A.; Tomuleasa, C.; Kacso, G. The androgen receptor remains a key player in metastatic hormone-refractory prostate cancer. Implications for new treatments. J. BUON 2014, 19, 357–364. [Google Scholar] [PubMed]
- Tilki, D.; Schaeffer, E.M.; Evans, C.P. Understanding Mechanisms of Resistance in Metastatic Castration-resistant Prostate Cancer: The Role of the Androgen Receptor. Eur. Urol. Focus 2016, 2, 499–505. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Fujimura, T.; Takayama, K.; Takahashi, S.; Inoue, S. Estrogen and Androgen Blockade for Advanced Prostate Cancer in the Era of Precision Medicine. Cancers 2018, 10, 29. [Google Scholar] [CrossRef] [Green Version]
- Aurilio, G.; Cimadamore, A.; Mazzucchelli, R.; Lopez-Beltran, A.; Verri, E.; Scarpelli, M.; Massari, F.; Cheng, L.; Santoni, M.; Montironi, R. Androgen Receptor Signaling Pathway in Prostate Cancer: From Genetics to Clinical Applications. Cells 2020, 9, 2653. [Google Scholar] [CrossRef]
- Messner, E.A.; Steele, T.M.; Tsamouri, M.M.; Hejazi, N.; Gao, A.C.; Mudryj, M.; Ghosh, P.M. The Androgen Receptor in Prostate Cancer: Effect of Structure, Ligands and Spliced Variants on Therapy. Biomedicines 2020, 8, 422. [Google Scholar] [CrossRef] [PubMed]
- Baba, Y.; Matsuo, H.; Schally, A.V. Structure of the porcine LH- and FSH-releasing hormone. II. Confirmation of the proposed structure by conventional sequential analyses. Biochem. Biophys. Res. Commun. 1971, 44, 459–463. [Google Scholar] [CrossRef]
- Schally, A.V.; Arimura, A.; Baba, Y.; Nair, R.M.; Matsuo, H.; Redding, T.W.; Debeljuk, L. Isolation and properties of the FSH and LH-releasing hormone. Biochem. Biophys. Res. Commun. 1971, 43, 393–399. [Google Scholar] [CrossRef]
- Conn, P.M.; Crowley, W.F., Jr. Gonadotropin-releasing hormone and its analogs. Annu. Rev. Med. 1994, 45, 391–405. [Google Scholar] [CrossRef]
- Harrison, G.S.; Wierman, M.E.; Nett, T.M.; Glode, L.M. Gonadotropin-releasing hormone and its receptor in normal and malignant cells. Endocr. Relat. Cancer 2004, 11, 725–748. [Google Scholar] [CrossRef]
- Millar, R.P. GnRHs and GnRH receptors. Anim. Reprod. Sci. 2005, 88, 5–28. [Google Scholar] [CrossRef]
- Tzoupis, H.; Nteli, A.; Androutsou, M.; Tselios, T. Gonadotropin Releasing Hormone and GnRH Receptor: Structure, Function and Drug Development. Curr. Med. Chem. 2019, 27, 6136. [Google Scholar] [CrossRef]
- Limonta, P.; Marelli, M.M.; Moretti, R.M. LHRH analogues as anticancer agents: Pituitary and extrapituitary sites of action. Expert Opin. Investig. Drugs 2001, 10, 709–720. [Google Scholar] [CrossRef]
- Limonta, P.; Moretti, R.M.; Montagnani Marelli, M.; Motta, M. The biology of gonadotropin hormone-releasing hormone: Role in the control of tumor growth and progression in humans. Front. Neuroendocrinol. 2003, 24, 279–295. [Google Scholar] [CrossRef]
- Moretti, R.M.; Marelli, M.M.; Groeninghen, J.C.v.; Motta, M.; Limonta, P. Inhibitory activity of luteinizing hormone-releasing hormone on tumor growth and progression. Endocr. Relat. Cancer 2003, 10, 161–167. [Google Scholar] [CrossRef] [Green Version]
- Marelli, M.M.; Moretti, R.M.; Caulier, J.J.; Motta, M.; Limonta, P. Gonadotropin-Releasing Hormone (GnRH) receptors in tumors: A new rationale for the therapeutical application of GnRH analogs in cancer patients? Curr. Cancer Drug Targets 2006, 6, 257–269. [Google Scholar] [CrossRef]
- Limonta, P.; Marelli, M.M.; Mai, S.; Motta, M.; Martini, L.; Moretti, R.M. GnRH Receptors in Cancer: From Cell Biology to Novel Targeted Therapeutic Strategies. Endocr. Rev. 2012, 33, 784–811. [Google Scholar] [CrossRef] [Green Version]
- Limonta, P.; Manea, M. Gonadotropin-releasing hormone receptors as molecular therapeutic targets in prostate cancer: Current options and emerging strategies. Cancer Treat. Rev. 2013, 39, 647. [Google Scholar] [CrossRef]
- Manea, M.; Marelli, M.M.; Moretti, R.M.; Maggi, R.; Marzagalli, M.; Limonta, P. Targeting hormonal signaling pathways in castration resistant prostate cancer. Recent Pat. Anticancer Drug Discov. 2014, 9, 267–285. [Google Scholar] [CrossRef]
- Limonta, P.; Marelli, M.M.; Moretti, R.; Marzagalli, M.; Fontana, F.; Maggi, R. GnRH in the human female reproductive axis. Vitam. Horm. 2018, 107, 27–66. [Google Scholar]
- Aguilar-Rojas, A.; Perez-Solis, M.A.; Maya-Nunez, G. The gonadotropin-releasing hormone system: Perspectives from reproduction to cancer (Review). Int. J. Oncol. 2016, 48, 861–868. [Google Scholar] [CrossRef]
- Grundker, C.; Emons, G. The Role of Gonadotropin-Releasing Hormone in Cancer Cell Proliferation and Metastasis. Front. Endocrinol. 2017, 8, 187. [Google Scholar] [CrossRef]
- Schally, A.V.; Block, N.L.; Rick, F.G. Discovery of LHRH and development of LHRH analogs for prostate cancer treatment. Prostate 2017, 77, 1036–1054. [Google Scholar] [CrossRef]
- Fontana, F.; Marzagalli, M.; Montagnani Marelli, M.; Raimondi, M.; Moretti, R.M.; Limonta, P. Gonadotropin-Releasing Hormone Receptors in Prostate Cancer: Molecular Aspects and Biological Functions. Int. J. Mol. Sci. 2020, 21, 9511. [Google Scholar] [CrossRef]
- Emons, G.; Grundker, C. The Role of Gonadotropin-Releasing Hormone (GnRH) in Endometrial Cancer. Cells 2021, 10, 292. [Google Scholar] [CrossRef]
- Grundker, C.; Emons, G. Role of Gonadotropin-Releasing Hormone (GnRH) in Ovarian Cancer. Cells 2021, 10, 437. [Google Scholar] [CrossRef]
- Contreras, H.R.; Lopez-Moncada, F.; Castellon, E.A. Cancer stem cell and mesenchymal cell cooperative actions in metastasis progression and hormone resistance in prostate cancer: Potential role of androgen and gonadotropinreleasing hormone receptors (Review). Int. J. Oncol. 2020, 56, 1075–1082. [Google Scholar] [CrossRef]
- Miyake, H.; Matsushita, Y.; Watanabe, H.; Tamura, K.; Motoyama, D.; Ito, T.; Sugiyama, T.; Otsuka, A. Comparative assessment of prognostic outcomes between first-generation antiandrogens and novel androgen-receptor-axis-targeted agents in patients with non-metastatic castration-resistant prostate cancer. Int. J. Clin. Oncol. 2019, 24, 842–847. [Google Scholar] [CrossRef]
- Altavilla, A.; Casadei, C.; Lolli, C.; Menna, C.; Ravaglia, G.; Gurioli, G.; Farolfi, A.; Brighi, N.; Conteduca, V.; Burgio, S.L.; et al. Enzalutamide for the treatment of nonmetastatic castration-resistant prostate cancer. Expert Opin. Pharmacother. 2020, 21, 2091–2099. [Google Scholar] [CrossRef]
- Crawford, E.D.; Stanton, W.; Mandair, D. Darolutamide: An Evidenced-Based Review of Its Efficacy and Safety in the Treatment of Prostate Cancer. Cancer Manag. Res. 2020, 12, 5667–5676. [Google Scholar] [CrossRef]
- Lavaud, P.; Dumont, C.; Thibault, C.; Albiges, L.; Baciarello, G.; Colomba, E.; Flippot, R.; Fuerea, A.; Loriot, Y.; Fizazi, K. Next-generation androgen receptor inhibitors in non-metastatic castration-resistant prostate cancer. Ther. Adv. Med. Oncol. 2020, 12, 1758835920978134. [Google Scholar] [CrossRef]
- Mori, K.; Miura, N.; Mostafaei, H.; Quhal, F.; Sari Motlagh, R.; Pradere, B.; Kimura, S.; Kimura, T.; Egawa, S.; Briganti, A.; et al. Sequential therapy of abiraterone and enzalutamide in castration-resistant prostate cancer: A systematic review and meta-analysis. Prostate Cancer Prostatic Dis. 2020, 23, 539–548. [Google Scholar] [CrossRef]
- Pyrgidis, N.; Vakalopoulos, I.; Sountoulides, P. Endocrine consequences of treatment with the new androgen receptor axis-targeted agents for advanced prostate cancer. Hormones 2020, 20, 73. [Google Scholar] [CrossRef]
- Cassinello, J.; Dominguez-Lubillo, T.; Gomez-Barrera, M.; Hernando, T.; Parra, R.; Asensio, I.; Casado, M.A.; Moreno, P. Optimal treatment sequencing of abiraterone acetate plus prednisone and enzalutamide in patients with castration-resistant metastatic prostate cancer: A systematic review and meta-analysis. Cancer Treat. Rev. 2021, 93, 102152. [Google Scholar] [CrossRef] [PubMed]
- Cai, Z.; Chen, W.; Zhang, J.; Li, H. Androgen receptor: What we know and what we expect in castration-resistant prostate cancer. Int. Urol. Nephrol. 2018, 50, 1753–1764. [Google Scholar] [CrossRef] [PubMed]
- Feng, Q.; He, B. Androgen Receptor Signaling in the Development of Castration-Resistant Prostate Cancer. Front. Oncol. 2019, 9, 858. [Google Scholar] [CrossRef] [Green Version]
- Mollica, V.; Di Nunno, V.; Cimadamore, A.; Lopez-Beltran, A.; Cheng, L.; Santoni, M.; Scarpelli, M.; Montironi, R.; Massari, F. Molecular Mechanisms Related to Hormone Inhibition Resistance in Prostate Cancer. Cells 2019, 8, 43. [Google Scholar] [CrossRef] [Green Version]
- Titus, M.A.; Schell, M.J.; Lih, F.B.; Tomer, K.B.; Mohler, J.L. Testosterone and dihydrotestosterone tissue levels in recurrent prostate cancer. Clin. Cancer Res. 2005, 11, 4653–4657. [Google Scholar] [CrossRef] [Green Version]
- Stanbrough, M.; Bubley, G.J.; Ross, K.; Golub, T.R.; Rubin, M.A.; Penning, T.M.; Febbo, P.G.; Balk, S.P. Increased expression of genes converting adrenal androgens to testosterone in androgen-independent prostate cancer. Cancer Res. 2006, 66, 2815–2825. [Google Scholar] [CrossRef] [Green Version]
- Cai, C.; Balk, S.P. Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy. Endocr. Relat. Cancer 2011, 18, R175–R182. [Google Scholar] [CrossRef] [Green Version]
- Kumagai, J.; Hofland, J.; Erkens-Schulze, S.; Dits, N.F.; Steenbergen, J.; Jenster, G.; Homma, Y.; de Jong, F.H.; van Weerden, W.M. Intratumoral conversion of adrenal androgen precursors drives androgen receptor-activated cell growth in prostate cancer more potently than de novo steroidogenesis. Prostate 2013, 73, 1636. [Google Scholar] [CrossRef]
- Montgomery, R.B.; Mostaghel, E.A.; Vessella, R.; Hess, D.L.; Kalhorn, T.F.; Higano, C.S.; True, L.D.; Nelson, P.S. Maintenance of intratumoral androgens in metastatic prostate cancer: A mechanism for castration-resistant tumor growth. Cancer Res. 2008, 68, 4447–4454. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mitsiades, N. A road map to comprehensive androgen receptor axis targeting for castration-resistant prostate cancer. Cancer Res. 2013, 73, 4599–4605. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rice, M.A.; Malhotra, S.V.; Stoyanova, T. Second-Generation Antiandrogens: From Discovery to Standard of Care in Castration Resistant Prostate Cancer. Front. Oncol. 2019, 9, 801. [Google Scholar] [CrossRef] [PubMed]
- Gourdin, T. Recent progress in treating advanced prostate cancer. Curr. Opin. Oncol. 2020, 32, 210–215. [Google Scholar] [CrossRef] [PubMed]
- Moussa, M.; Papatsoris, A.; Abou Chakra, M.; Sryropoulou, D.; Dellis, A. Pharmacotherapeutic strategies for castrate-resistant prostate cancer. Expert Opin. Pharmacother. 2020, 21, 1431–1448. [Google Scholar] [CrossRef] [PubMed]
- Koivisto, P.; Kononen, J.; Palmberg, C.; Tammela, T.; Hyytinen, E.; Isola, J.; Trapman, J.; Cleutjens, K.; Noordzij, A.; Visakorpi, T.; et al. Androgen receptor gene amplification: A possible molecular mechanism for androgen deprivation therapy failure in prostate cancer. Cancer Res. 1997, 57, 314–319. [Google Scholar] [PubMed]
- Palmberg, C.; Koivisto, P.; Kakkola, L.; Tammela, T.L.; Kallioniemi, O.P.; Visakorpi, T. Androgen receptor gene amplification at primary progression predicts response to combined androgen blockade as second line therapy for advanced prostate cancer. J. Urol. 2000, 164, 1992–1995. [Google Scholar] [CrossRef]
- Kohli, M.; Li, J.; Du, M.; Hillman, D.W.; Dehm, S.M.; Tan, W.; Carlson, R.; Campion, M.B.; Wang, L.; Wang, L.; et al. Prognostic association of plasma cell-free DNA-based androgen receptor amplification and circulating tumor cells in pre-chemotherapy metastatic castration-resistant prostate cancer patients. Prostate Cancer Prostatic Dis. 2018, 21, 411–418. [Google Scholar] [CrossRef]
- Leversha, M.A.; Han, J.; Asgari, Z.; Danila, D.C.; Lin, O.; Gonzalez-Espinoza, R.; Anand, A.; Lilja, H.; Heller, G.; Fleisher, M.; et al. Fluorescence in situ hybridization analysis of circulating tumor cells in metastatic prostate cancer. Clin. Cancer Res. 2009, 15, 2091–2209. [Google Scholar] [CrossRef] [Green Version]
- Azad, A.A.; Volik, S.V.; Wyatt, A.W.; Haegert, A.; Le Bihan, S.; Bell, R.H.; Anderson, S.A.; McConeghy, B.; Shukin, R.; Bazov, J.; et al. Androgen Receptor Gene Aberrations in Circulating Cell-Free DNA: Biomarkers of Therapeutic Resistance in Castration-Resistant Prostate Cancer. Clin. Cancer Res. 2015, 21, 2315–2324. [Google Scholar] [CrossRef] [Green Version]
- Salvi, S.; Casadio, V.; Conteduca, V.; Lolli, C.; Gurioli, G.; Martignano, F.; Schepisi, G.; Testoni, S.; Scarpi, E.; Amadori, D.; et al. Circulating AR copy number and outcome to enzalutamide in docetaxel-treated metastatic castration-resistant prostate cancer. Oncotarget 2016, 7, 37839–37845. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Gao, W.; Bohl, C.E.; Dalton, J.T. Chemistry and structural biology of androgen receptor. Chem. Rev. 2005, 105, 3352–3370. [Google Scholar] [CrossRef] [Green Version]
- Matsumoto, T.; Sakari, M.; Okada, M.; Yokoyama, A.; Takahashi, S.; Kouzmenko, A.; Kato, S. The androgen receptor in health and disease. Annu. Rev. Physiol. 2013, 75, 201–224. [Google Scholar] [CrossRef] [PubMed]
- Tan, M.H.; Li, J.; Xu, H.E.; Melcher, K.; Yong, E.L. Androgen receptor: Structure, role in prostate cancer and drug discovery. Acta Pharmacol. Sin. 2015, 36, 3–23. [Google Scholar] [CrossRef] [Green Version]
- Taplin, M.E.; Rajeshkumar, B.; Halabi, S.; Werner, C.P.; Woda, B.A.; Picus, J.; Stadler, W.; Hayes, D.F.; Kantoff, P.W.; Vogelzang, N.J.; et al. Androgen receptor mutations in androgen-independent prostate cancer: Cancer and Leukemia Group B Study 9663. J. Clin. Oncol. 2003, 21, 2673–2678. [Google Scholar] [CrossRef] [PubMed]
- Robinson, D.; Van Allen, E.M.; Wu, Y.M.; Schultz, N.; Lonigro, R.J.; Mosquera, J.M.; Montgomery, B.; Taplin, M.E.; Pritchard, C.C.; Attard, G.; et al. Integrative clinical genomics of advanced prostate cancer. Cell 2015, 161, 1215–1228. [Google Scholar] [CrossRef] [Green Version]
- Taplin, M.E.; Bubley, G.J.; Shuster, T.D.; Frantz, M.E.; Spooner, A.E.; Ogata, G.K.; Keer, H.N.; Balk, S.P. Mutation of the androgen-receptor gene in metastatic androgen-independent prostate cancer. N. Engl. J. Med. 1995, 332, 1393–1398. [Google Scholar] [CrossRef]
- Joseph, J.D.; Lu, N.; Qian, J.; Sensintaffar, J.; Shao, G.; Brigham, D.; Moon, M.; Maneval, E.C.; Chen, I.; Darimont, B.; et al. A clinically relevant androgen receptor mutation confers resistance to second-generation antiandrogens enzalutamide and ARN-509. Cancer Discov. 2013, 3, 1020–1029. [Google Scholar] [CrossRef] [Green Version]
- Korpal, M.; Korn, J.M.; Gao, X.; Rakiec, D.P.; Ruddy, D.A.; Doshi, S.; Yuan, J.; Kovats, S.G.; Kim, S.; Cooke, V.G.; et al. An F876L mutation in androgen receptor confers genetic and phenotypic resistance to MDV3100 (enzalutamide). Cancer Discov. 2013, 3, 1030–1043. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lallous, N.; Volik, S.V.; Awrey, S.; Leblanc, E.; Tse, R.; Murillo, J.; Singh, K.; Azad, A.A.; Wyatt, A.W.; LeBihan, S.; et al. Functional analysis of androgen receptor mutations that confer anti-androgen resistance identified in circulating cell-free DNA from prostate cancer patients. Genome Biol. 2016, 17, 10. [Google Scholar] [CrossRef] [Green Version]
- Prekovic, S.; van Royen, M.E.; Voet, A.R.; Geverts, B.; Houtman, R.; Melchers, D.; Zhang, K.Y.; Van den Broeck, T.; Smeets, E.; Spans, L.; et al. The Effect of F877L and T878A Mutations on Androgen Receptor Response to Enzalutamide. Mol. Cancer Ther. 2016, 15, 1702–1712. [Google Scholar] [CrossRef] [Green Version]
- Miyamoto, H.; Yeh, S.; Lardy, H.; Messing, E.; Chang, C. Delta5-androstenediol is a natural hormone with androgenic activity in human prostate cancer cells. Proc. Natl. Acad. Sci. USA 1998, 95, 11083–11088. [Google Scholar] [CrossRef] [Green Version]
- Zhao, X.Y.; Malloy, P.J.; Krishnan, A.V.; Swami, S.; Navone, N.M.; Peehl, D.M.; Feldman, D. Glucocorticoids can promote androgen-independent growth of prostate cancer cells through a mutated androgen receptor. Nat. Med. 2000, 6, 703–706. [Google Scholar] [CrossRef] [PubMed]
- van de Wijngaart, D.J.; Molier, M.; Lusher, S.J.; Hersmus, R.; Jenster, G.; Trapman, J.; Dubbink, H.J. Systematic structure-function analysis of androgen receptor Leu701 mutants explains the properties of the prostate cancer mutant L701H. J. Biol. Chem. 2010, 285, 5097–5105. [Google Scholar] [CrossRef] [Green Version]
- Steinkamp, M.P.; O’Mahony, O.A.; Brogley, M.; Rehman, H.; Lapensee, E.W.; Dhanasekaran, S.; Hofer, M.D.; Kuefer, R.; Chinnaiyan, A.; Rubin, M.A.; et al. Treatment-dependent androgen receptor mutations in prostate cancer exploit multiple mechanisms to evade therapy. Cancer Res. 2009, 69, 4434–4442. [Google Scholar] [CrossRef] [Green Version]
- Barbieri, C.E.; Baca, S.C.; Lawrence, M.S.; Demichelis, F.; Blattner, M.; Theurillat, J.P.; White, T.A.; Stojanov, P.; Van Allen, E.; Stransky, N.; et al. Exome sequencing identifies recurrent SPOP, FOXA1 and MED12 mutations in prostate cancer. Nat. Genet. 2012, 44, 685–689. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Conteduca, V.; Wetterskog, D.; Sharabiani, M.T.A.; Grande, E.; Fernandez-Perez, M.P.; Jayaram, A.; Salvi, S.; Castellano, D.; Romanel, A.; Lolli, C.; et al. Androgen receptor gene status in plasma DNA associates with worse outcome on enzalutamide or abiraterone for castration-resistant prostate cancer: A multi-institution correlative biomarker study. Ann. Oncol. 2017, 28, 1508–1516. [Google Scholar] [CrossRef] [PubMed]
- Sumiyoshi, T.; Mizuno, K.; Yamasaki, T.; Miyazaki, Y.; Makino, Y.; Okasho, K.; Li, X.; Utsunomiya, N.; Goto, T.; Kobayashi, T.; et al. Clinical utility of androgen receptor gene aberrations in circulating cell-free DNA as a biomarker for treatment of castration-resistant prostate cancer. Sci. Rep. 2019, 9, 4030. [Google Scholar] [CrossRef] [Green Version]
- Ledet, E.M.; Lilly, M.B.; Sonpavde, G.; Lin, E.; Nussenzveig, R.H.; Barata, P.C.; Yandell, M.; Nagy, R.J.; Kiedrowski, L.; Agarwal, N.; et al. Comprehensive Analysis of AR Alterations in Circulating Tumor DNA from Patients with Advanced Prostate Cancer. Oncologist 2020, 25, 327–333. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Haile, S.; Sadar, M.D. Androgen receptor and its splice variants in prostate cancer. Cell Mol. Life Sci. 2011, 68, 3971–3981. [Google Scholar] [CrossRef] [Green Version]
- Lu, C.; Luo, J. Decoding the androgen receptor splice variants. Translat. Androl. Urol. 2013, 2, 178–186. [Google Scholar]
- Bryce, A.H.; Antonarakis, E.S. Androgen receptor splice variant 7 in castration-resistant prostate cancer: Clinical considerations. Int. J. Urol. 2016, 23, 646–653. [Google Scholar] [CrossRef]
- Lu, C.; Brown, L.C.; Antonarakis, E.S.; Armstrong, A.J.; Luo, J. Androgen receptor variant-driven prostate cancer II: Advances in laboratory investigations. Prostate Cancer Prostatic Dis. 2020, 23, 381–397. [Google Scholar] [CrossRef] [PubMed]
- Zhu, Y.; Luo, J. Regulation of androgen receptor variants in prostate cancer. Asian J. Urol. 2020, 7, 251–257. [Google Scholar] [CrossRef] [PubMed]
- Luo, J. Development of AR-V7 as a putative treatment selection marker for metastatic castration-resistant prostate cancer. Asian J. Androl. 2016, 18, 580–585. [Google Scholar] [CrossRef]
- Li, Y.; Chan, S.C.; Brand, L.J.; Hwang, T.H.; Silverstein, K.A.; Dehm, S.M. Androgen receptor splice variants mediate enzalutamide resistance in castration-resistant prostate cancer cell lines. Cancer Res. 2013, 73, 483–489. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mostaghel, E.A.; Marck, B.T.; Plymate, S.R.; Vessella, R.L.; Balk, S.; Matsumoto, A.M.; Nelson, P.S.; Montgomery, R.B. Resistance to CYP17A1 inhibition with abiraterone in castration-resistant prostate cancer: Induction of steroidogenesis and androgen receptor splice variants. Clin. Cancer Res. 2011, 17, 5913–5925. [Google Scholar] [CrossRef] [Green Version]
- Sarwar, M.; Semenas, J.; Miftakhova, R.; Simoulis, A.; Robinson, B.; Gjorloff Wingren, A.; Mongan, N.P.; Heery, D.M.; Johnsson, H.; Abrahamsson, P.A.; et al. Targeted suppression of AR-V7 using PIP5K1alpha inhibitor overcomes enzalutamide resistance in prostate cancer cells. Oncotarget 2016, 7, 63065–63081. [Google Scholar] [CrossRef] [Green Version]
- Cao, Q.; Song, Z.; Ruan, H.; Wang, C.; Yang, X.; Bao, L.; Wang, K.; Cheng, G.; Xu, T.; Xiao, W.; et al. Targeting the KIF4A/AR Axis to Reverse Endocrine Therapy Resistance in Castration-resistant Prostate Cancer. Clin. Cancer Res. 2020, 26, 1516–1528. [Google Scholar] [CrossRef] [Green Version]
- Sun, S.; Sprenger, C.C.; Vessella, R.L.; Haugk, K.; Soriano, K.; Mostaghel, E.A.; Page, S.T.; Coleman, I.M.; Nguyen, H.M.; Sun, H.; et al. Castration resistance in human prostate cancer is conferred by a frequently occurring androgen receptor splice variant. J. Clin. Investig. 2010, 120, 2715–2730. [Google Scholar] [CrossRef] [Green Version]
- Hornberg, E.; Ylitalo, E.B.; Crnalic, S.; Antti, H.; Stattin, P.; Widmark, A.; Bergh, A.; Wikstrom, P. Expression of androgen receptor splice variants in prostate cancer bone metastases is associated with castration-resistance and short survival. PLoS ONE 2011, 6, e19059. [Google Scholar] [CrossRef] [Green Version]
- Zhang, X.; Morrissey, C.; Sun, S.; Ketchandji, M.; Nelson, P.S.; True, L.D.; Vakar-Lopez, F.; Vessella, R.L.; Plymate, S.R. Androgen receptor variants occur frequently in castration resistant prostate cancer metastases. PLoS ONE 2011, 6, e27970. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Welti, J.; Rodrigues, D.N.; Sharp, A.; Sun, S.; Lorente, D.; Riisnaes, R.; Figueiredo, I.; Zafeiriou, Z.; Rescigno, P.; de Bono, J.S.; et al. Analytical Validation and Clinical Qualification of a New Immunohistochemical Assay for Androgen Receptor Splice Variant-7 Protein Expression in Metastatic Castration-resistant Prostate Cancer. Eur. Urol. 2016, 70, 599–608. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sharp, A.; Coleman, I.; Yuan, W.; Sprenger, C.; Dolling, D.; Rodrigues, D.N.; Russo, J.W.; Figueiredo, I.; Bertan, C.; Seed, G.; et al. Androgen receptor splice variant-7 expression emerges with castration resistance in prostate cancer. J. Clin. Investig. 2019, 129, 192–208. [Google Scholar] [CrossRef] [Green Version]
- Antonarakis, E.S.; Lu, C.; Wang, H.; Luber, B.; Nakazawa, M.; Roeser, J.C.; Chen, Y.; Mohammad, T.A.; Chen, Y.; Fedor, H.L.; et al. AR-V7 and resistance to enzalutamide and abiraterone in prostate cancer. N. Engl. J. Med. 2014, 371, 1028–1038. [Google Scholar] [CrossRef] [Green Version]
- Strati, A.; Zavridou, M.; Bournakis, E.; Mastoraki, S.; Lianidou, E. Expression pattern of androgen receptors, AR-V7 and AR-567es, in circulating tumor cells and paired plasma-derived extracellular vesicles in metastatic castration resistant prostate cancer. Analyst 2019, 144, 6671–6680. [Google Scholar] [CrossRef] [PubMed]
- Foroni, C.; Zarovni, N.; Bianciardi, L.; Bernardi, S.; Triggiani, L.; Zocco, D.; Venturella, M.; Chiesi, A.; Valcamonico, F.; Berruti, A. When Less Is More: Specific Capture and Analysis of Tumor Exosomes in Plasma Increases the Sensitivity of Liquid Biopsy for Comprehensive Detection of Multiple Androgen Receptor Phenotypes in Advanced Prostate Cancer Patients. Biomedicines 2020, 8, 131. [Google Scholar] [CrossRef] [PubMed]
- Zhang, T.; Karsh, L.I.; Nissenblatt, M.J.; Canfield, S.E. Androgen Receptor Splice Variant, AR-V7, as a Biomarker of Resistance to Androgen Axis-Targeted Therapies in Advanced Prostate Cancer. Clin. Genitourin. Cancer 2020, 18, 1–10. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Zavridou, M.; Strati, A.; Bournakis, E.; Smilkou, S.; Tserpeli, V.; Lianidou, E. Prognostic Significance of Gene Expression and DNA Methylation Markers in Circulating Tumor Cells and Paired Plasma Derived Exosomes in Metastatic Castration Resistant Prostate Cancer. Cancers 2021, 13, 780. [Google Scholar] [CrossRef] [PubMed]
- Ware, K.E.; Garcia-Blanco, M.A.; Armstrong, A.J.; Dehm, S.M. Biologic and clinical significance of androgen receptor variants in castration resistant prostate cancer. Endocr. Relat. Cancer 2014, 21, T87–T103. [Google Scholar] [CrossRef]
- Kallio, H.M.L.; Hieta, R.; Latonen, L.; Brofeldt, A.; Annala, M.; Kivinummi, K.; Tammela, T.L.; Nykter, M.; Isaacs, W.B.; Lilja, H.G.; et al. Constitutively active androgen receptor splice variants AR-V3, AR-V7 and AR-V9 are co-expressed in castration-resistant prostate cancer metastases. Br. J. Cancer 2018, 119, 347–356. [Google Scholar] [CrossRef] [Green Version]
- Tagawa, S.T.; Antonarakis, E.S.; Gjyrezi, A.; Galletti, G.; Kim, S.; Worroll, D.; Stewart, J.; Zaher, A.; Szatrowski, T.P.; Ballman, K.V.; et al. Expression of AR-V7 and ARv(567es) in Circulating Tumor Cells Correlates with Outcomes to Taxane Therapy in Men with Metastatic Prostate Cancer Treated in TAXYNERGY. Clin. Cancer Res. 2019, 25, 1880–1888. [Google Scholar] [CrossRef] [Green Version]
- Nagandla, H.; Robertson, M.J.; Putluri, V.; Putluri, N.; Coarfa, C.; Weigel, N.L. Isoform-specific Activities of Androgen Receptor and its Splice Variants in Prostate Cancer Cells. Endocrinology 2021, 162, bqaa227. [Google Scholar] [CrossRef] [PubMed]
- Yang, J.C.; Ok, J.H.; Busby, J.E.; Borowsky, A.D.; Kung, H.J.; Evans, C.P. Aberrant activation of androgen receptor in a new neuropeptide-autocrine model of androgen-insensitive prostate cancer. Cancer Res. 2009, 69, 151–160. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Heemers, H.V.; Tindall, D.J. Androgen receptor (AR) coregulators: A diversity of functions converging on and regulating the AR transcriptional complex. Endocr. Rev. 2007, 28, 778–808. [Google Scholar] [CrossRef] [Green Version]
- Chandrasekar, T.; Yang, J.C.; Gao, A.C.; Evans, C.P. Mechanisms of resistance in castration-resistant prostate cancer (CRPC). Translat. Androl. Urol. 2015, 4, 365–380. [Google Scholar]
- Foley, C.; Mitsiades, N. Moving Beyond the Androgen Receptor (AR): Targeting AR-Interacting Proteins to Treat Prostate Cancer. Horm. Cancer 2016, 7, 84–103. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Obinata, D.; Takayama, K.; Takahashi, S.; Inoue, S. Crosstalk of the Androgen Receptor with Transcriptional Collaborators: Potential Therapeutic Targets for Castration-Resistant Prostate Cancer. Cancers 2017, 9, 22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bishop, J.L.; Thaper, D.; Vahid, S.; Davies, A.; Ketola, K.; Kuruma, H.; Jama, R.; Nip, K.M.; Angeles, A.; Johnson, F.; et al. The Master Neural Transcription Factor BRN2 Is an Androgen Receptor-Suppressed Driver of Neuroendocrine Differentiation in Prostate Cancer. Cancer Discov. 2017, 7, 54–71. [Google Scholar] [CrossRef] [Green Version]
- Teng, M.; Zhou, S.; Cai, C.; Lupien, M.; He, H.H. Pioneer of prostate cancer: Past, present and the future of FOXA1. Protein Cell 2021, 12, 29–38. [Google Scholar] [CrossRef] [PubMed]
- Copeland, B.T.; Pal, S.K.; Bolton, E.C.; Jones, J.O. The androgen receptor malignancy shift in prostate cancer. Prostate 2018, 78, 521–531. [Google Scholar] [CrossRef] [PubMed]
- Hankey, W.; Chen, Z.; Wang, Q. Shaping Chromatin States in Prostate Cancer by Pioneer Transcription Factors. Cancer Res. 2020, 80, 2427–2436. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hermanson, O.; Glass, C.K.; Rosenfeld, M.G. Nuclear receptor coregulators: Multiple modes of modification. Trends Endocrinol. Metab. 2002, 13, 55–60. [Google Scholar] [CrossRef]
- Wang, Q.; Carroll, J.S.; Brown, M. Spatial and temporal recruitment of androgen receptor and its coactivators involves chromosomal looping and polymerase tracking. Mol. Cell 2005, 19, 631–642. [Google Scholar] [CrossRef]
- Chung, A.C.; Zhou, S.; Liao, L.; Tien, J.C.; Greenberg, N.M.; Xu, J. Genetic ablation of the amplified-in-breast cancer 1 inhibits spontaneous prostate cancer progression in mice. Cancer Res. 2007, 67, 5965–5975. [Google Scholar] [CrossRef] [Green Version]
- Xu, J.; Wu, R.C.; O’Malley, B.W. Normal and cancer-related functions of the p160 steroid receptor co-activator (SRC) family. Nat. Rev. Cancer 2009, 9, 615–630. [Google Scholar] [CrossRef] [Green Version]
- Taylor, B.S.; Schultz, N.; Hieronymus, H.; Gopalan, A.; Xiao, Y.; Carver, B.S.; Arora, V.K.; Kaushik, P.; Cerami, E.; Reva, B.; et al. Integrative genomic profiling of human prostate cancer. Cancer Cell 2010, 18, 11–22. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Ueda, T.; Mawji, N.R.; Bruchovsky, N.; Sadar, M.D. Ligand-independent activation of the androgen receptor by interleukin-6 and the role of steroid receptor coactivator-1 in prostate cancer cells. J. Biol. Chem. 2002, 277, 38087–38094. [Google Scholar] [CrossRef] [Green Version]
- Fujimoto, N.; Miyamoto, H.; Mizokami, A.; Harada, S.; Nomura, M.; Ueta, Y.; Sasaguri, T.; Matsumoto, T. Prostate cancer cells increase androgen sensitivity by increase in nuclear androgen receptor and androgen receptor coactivators; a possible mechanism of hormone-resistance of prostate cancer cells. Cancer Investig. 2007, 25, 32–37. [Google Scholar] [CrossRef] [PubMed]
- Karpf, A.R.; Bai, S.; James, S.R.; Mohler, J.L.; Wilson, E.M. Increased expression of androgen receptor coregulator MAGE-11 in prostate cancer by DNA hypomethylation and cyclic AMP. Mol. Cancer Res. 2009, 7, 523–535. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Taylor, L.G.; Canfield, S.E.; Du, X.L. Review of major adverse effects of androgen-deprivation therapy in men with prostate cancer. Cancer 2009, 115, 2388–2399. [Google Scholar] [CrossRef]
- Wu, Y.; Rosenberg, J.E.; Taplin, M.E. Novel agents and new therapeutics in castration-resistant prostate cancer. Curr. Opin. Oncol. 2011, 23, 290–296. [Google Scholar] [CrossRef] [PubMed]
- Klotz, L. Degarelix acetate for the treatment of prostate cancer. Drugs Today 2009, 45, 725–730. [Google Scholar] [CrossRef]
- Van Poppel, H.; Abrahamsson, P.A. Considerations for the use of gonadotropin-releasing hormone agonists and antagonists in patients with prostate cancer. Int. J. Urol. 2020, 27, 830–837. [Google Scholar] [CrossRef]
- Abufaraj, M.; Iwata, T.; Kimura, S.; Haddad, A.; Al-Ani, H.; Abusubaih, L.; Moschini, M.; Briganti, A.; Karakiewicz, P.I.; Shariat, S.F. Differential Impact of Gonadotropin-releasing Hormone Antagonist Versus Agonist on Clinical Safety and Oncologic Outcomes on Patients with Metastatic Prostate Cancer: A Meta-analysis of Randomized Controlled Trials. Eur. Urol. 2021, 79, 44–53. [Google Scholar] [CrossRef] [PubMed]
- Liu, Y.F.; Fu, S.Q.; Yan, Y.C.; Gong, B.B.; Xie, W.J.; Yang, X.R.; Sun, T.; Ma, M. Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer. Drug Des. Dev. Ther. 2021, 15, 639–649. [Google Scholar] [CrossRef]
- Schally, A.V.; Comaru-Schally, A.M.; Nagy, A.; Kovacs, M.; Szepeshazi, K.; Plonowski, A.; Varga, J.L.; Halmos, G. Hypothalamic hormones and cancer. Front. Neuroendocrinol. 2001, 22, 248–291. [Google Scholar] [CrossRef]
- Grundker, C.; Gunthert, A.R.; Westphalen, S.; Emons, G. Biology of the gonadotropin-releasing hormone system in gynecological cancers. Eur. J. Endocrinol. 2002, 146, 1–14. [Google Scholar] [CrossRef] [Green Version]
- So, W.K.; Cheng, J.C.; Poon, S.L.; Leung, P.C. Gonadotropin-releasing hormone and ovarian cancer: A functional and mechanistic overview. FEBS J. 2008, 275, 5496–5511. [Google Scholar] [CrossRef]
- Schneider, J.S.; Rissman, E.F. Gonadotropin-releasing hormone II: A multi-purpose neuropeptide. Integr. Compar. Biol. 2008, 48, 588–595. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cheon, K.W.; Lee, H.S.; Parhar, I.S.; Kang, I.S. Expression of the second isoform of gonadotrophin-releasing hormone (GnRH-II) in human endometrium throughout the menstrual cycle. Mol. Hum. Reprod. 2001, 7, 447–452. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grundker, C.; Gunthert, A.R.; Millar, R.P.; Emons, G. Expression of gonadotropin-releasing hormone II (GnRH-II) receptor in human endometrial and ovarian cancer cells and effects of GnRH-II on tumor cell proliferation. J. Clin. Endocrinol. Metab. 2002, 87, 1427–1430. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Millar, R.P. GnRH II and type II GnRH receptors. Trends Endocrinol. Metab. 2003, 14, 35–43. [Google Scholar] [CrossRef]
- Neill, J.D.; Musgrove, L.C.; Duck, L.W. Newly recognized GnRH receptors: Function and relative role. Trends Endocrinol. Metab. 2004, 15, 383–392. [Google Scholar] [CrossRef]
- Cheng, C.K.; Leung, P.C. Molecular biology of gonadotropin-releasing hormone (GnRH)-I, GnRH-II, and their receptors in humans. Endocr. Rev. 2005, 26, 283–306. [Google Scholar] [CrossRef]
- Grundker, C.; Fost, C.; Fister, S.; Nolte, N.; Gunthert, A.R.; Emons, G. Gonadotropin-releasing hormone type II antagonist induces apoptosis in MCF-7 and triple-negative MDA-MB-231 human breast cancer cells in vitro and in vivo. Breast Cancer Res. 2010, 12, R49. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Sower, S.A.; Chiang, Y.C.; Lovas, S.; Conlon, J.M. Primary structure and biological activity of a third gonadotropin-releasing hormone from lamprey brain. Endocrinology 1993, 132, 1125–1131. [Google Scholar] [CrossRef] [PubMed]
- Kovacs, M.; Vincze, B.; Horvath, J.E.; Seprodi, J. Structure-activity study on the LH- and FSH-releasing and anticancer effects of gonadotropin-releasing hormone (GnRH)-III analogs. Peptides 2007, 28, 821–829. [Google Scholar] [CrossRef] [PubMed]
- Limonta, P.; Dondi, D.; Moretti, R.M.; Fermo, D.; Garattini, E.; Motta, M. Expression of luteinizing hormone-releasing hormone mRNA in the human prostatic cancer cell line LNCaP. J. Clin. Endocrinol. Metab. 1993, 76, 797–800. [Google Scholar]
- Ohno, T.; Imai, A.; Furui, T.; Takahashi, K.; Tamaya, T. Presence of gonadotropin-releasing hormone and its messenger ribonucleic acid in human ovarian epithelial carcinoma. Am. J. Obstet. Gynecol. 1993, 169, 605–610. [Google Scholar] [CrossRef]
- Dondi, D.; Limonta, P.; Moretti, R.M.; Marelli, M.M.; Garattini, E.; Motta, M. Antiproliferative effects of luteinizing hormone-releasing hormone (LHRH) agonists on human androgen-independent prostate cancer cell line DU 145: Evidence for an autocrine-inhibitory LHRH loop. Cancer Res. 1994, 54, 4091–4095. [Google Scholar] [PubMed]
- Irmer, G.; Burger, C.; Ortmann, O.; Schulz, K.D.; Emons, G. Expression of luteinizing hormone releasing hormone and its mRNA in human endometrial cancer cell lines. J. Clin. Endocrinol. Metab. 1994, 79, 916–919. [Google Scholar] [PubMed]
- Irmer, G.; Burger, C.; Muller, R.; Ortmann, O.; Peter, U.; Kakar, S.S.; Neill, J.D.; Schulz, K.D.; Emons, G. Expression of the messenger RNAs for luteinizing hormone-releasing hormone (LHRH) and its receptor in human ovarian epithelial carcinoma. Cancer Res. 1995, 55, 817–822. [Google Scholar]
- Kakar, S.S.; Musgrove, L.C.; Devor, D.C.; Sellers, J.C.; Neill, J.D. Cloning, sequencing, and expression of human gonadotropin releasing hormone (GnRH) receptor. Biochem. Biophys. Res. Commun. 1992, 189, 289–295. [Google Scholar] [CrossRef]
- Neill, J.D. GnRH and GnRH receptor genes in the human genome. Endocrinology 2002, 143, 737–743. [Google Scholar] [CrossRef]
- Kakar, S.S.; Malik, M.T.; Winters, S.J.; Mazhawidza, W. Gonadotropin-releasing hormone receptors: Structure, expression, and signaling transduction. Vitam. Horm. 2004, 69, 151–207. [Google Scholar]
- Millar, R.P.; Lu, Z.L.; Pawson, A.J.; Flanagan, C.A.; Morgan, K.; Maudsley, S.R. Gonadotropin-releasing hormone receptors. Endocr. Rev. 2004, 25, 235–275. [Google Scholar] [CrossRef] [Green Version]
- McArdle, C.A.; Franklin, J.; Green, L.; Hislop, J.N. Signalling, cycling and desensitisation of gonadotrophin-releasing hormone receptors. J. Endocrinol. 2002, 173, 1–11. [Google Scholar] [CrossRef] [Green Version]
- Kraus, S.; Naor, Z.; Seger, R. Intracellular signaling pathways mediated by the gonadotropin-releasing hormone (GnRH) receptor. Arch. Med. Res. 2001, 32, 499–509. [Google Scholar] [CrossRef]
- Aguilar-Rojas, A.; Huerta-Reyes, M. Human gonadotropin-releasing hormone receptor-activated cellular functions and signaling pathways in extra-pituitary tissues and cancer cells (Review). Oncol. Rep. 2009, 22, 981–990. [Google Scholar] [CrossRef] [PubMed]
- McArdle, C.A. Gonadotropin-releasing hormone receptor signaling: Biased and unbiased. Mini Rev. Med. Chem. 2012, 12, 841–850. [Google Scholar] [CrossRef] [PubMed]
- Naor, Z.; Huhtaniemi, I. Interactions of the GnRH receptor with heterotrimeric G proteins. Front. Neuroendocrinol. 2013, 34, 88–94. [Google Scholar] [CrossRef]
- Janjic, M.M.; Stojilkovic, S.S.; Bjelobaba, I. Intrinsic and Regulated Gonadotropin-Releasing Hormone Receptor Gene Transcription in Mammalian Pituitary Gonadotrophs. Front. Endocrinol. 2017, 8, 221. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Limonta, P.; Moretti, R.M.; Marelli, M.M.; Dondi, D.; Parenti, M.; Motta, M. The luteinizing hormone-releasing hormone receptor in human prostate cancer cells: Messenger ribonucleic acid expression, molecular size, and signal transduction pathway. Endocrinology 1999, 140, 5250–5256. [Google Scholar] [CrossRef]
- Qayum, A.; Gullick, W.; Clayton, R.C.; Sikora, K.; Waxman, J. The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors. Br. J. Cancer 1990, 62, 96–99. [Google Scholar] [CrossRef] [Green Version]
- Srkalovic, G.; Bokser, L.; Radulovic, S.; Korkut, E.; Schally, A.V. Receptors for luteinizing hormone-releasing hormone (LHRH) in Dunning R3327 prostate cancers and rat anterior pituitaries after treatment with a sustained delivery system of LHRH antagonist SB-75. Endocrinology 1990, 127, 3052–3060. [Google Scholar] [CrossRef] [PubMed]
- Limonta, P.; Dondi, D.; Moretti, R.M.; Maggi, R.; Motta, M. Antiproliferative effects of luteinizing hormone-releasing hormone agonists on the human prostatic cancer cell line LNCaP. J. Clin. Endocrinol. Metab. 1992, 75, 207–212. [Google Scholar] [PubMed]
- Pinski, J.; Reile, H.; Halmos, G.; Groot, K.; Schally, A.V. Inhibitory effects of analogs of luteinizing hormone-releasing hormone on the growth of the androgen-independent Dunning R-3327-AT-1 rat prostate cancer. Int. J. Cancer 1994, 59, 51–55. [Google Scholar] [CrossRef] [PubMed]
- Franklin, J.; Hislop, J.; Flynn, A.; McArdle, C.A. Signalling and anti-proliferative effects mediated by gonadotrophin-releasing hormone receptors after expression in prostate cancer cells using recombinant adenovirus. J. Endocrinol. 2003, 176, 275–284. [Google Scholar] [CrossRef]
- Limonta, P.; Dondi, D.; Marelli, M.M.; Moretti, R.M.; Negri-Cesi, P.; Motta, M. Growth of the androgen-dependent tumor of the prostate: Role of androgens and of locally expressed growth modulatory factors. J. Steroid Biochem. Mol. Biol. 1995, 53, 401–405. [Google Scholar] [CrossRef]
- Marelli, M.M.; Moretti, R.M.; Dondi, D.; Motta, M.; Limonta, P. Luteinizing hormone-releasing hormone agonists interfere with the mitogenic activity of the insulin-like growth factor system in androgen-independent prostate cancer cells. Endocrinology 1999, 140, 329–334. [Google Scholar] [CrossRef]
- Bahk, J.Y.; Hyun, J.S.; Lee, H.; Kim, M.O.; Cho, G.J.; Lee, B.H.; Choi, W.S. Expression of gonadotropin-releasing hormone (GnRH) and GnRH receptor mRNA in prostate cancer cells and effect of GnRH on the proliferation of prostate cancer cells. Urol. Res. 1998, 26, 259–264. [Google Scholar] [CrossRef] [PubMed]
- Halmos, G.; Arencibia, J.M.; Schally, A.V.; Davis, R.; Bostwick, D.G. High incidence of receptors for luteinizing hormone-releasing hormone (LHRH) and LHRH receptor gene expression in human prostate cancers. J. Urol. 2000, 163, 623–629. [Google Scholar] [CrossRef]
- Straub, B.; Muller, M.; Krause, H.; Schrader, M.; Goessl, C.; Heicappell, R.; Miller, K. Increased incidence of luteinizing hormone-releasing hormone receptor gene messenger RNA expression in hormone-refractory human prostate cancers. Clin. Cancer Res. 2001, 7, 2340–2343. [Google Scholar] [PubMed]
- Szabo, J.; Vegh, A.; Racz, G.; Szende, B. Immunohistochemical demonstration of gonadotropin-releasing hormone receptors in prostate carcinoma. Urol. Oncol. 2005, 23, 399–401. [Google Scholar] [CrossRef] [PubMed]
- Morgan, K.; Conklin, D.; Pawson, A.J.; Sellar, R.; Ott, T.R.; Millar, R.P. A transcriptionally active human type II gonadotropin-releasing hormone receptor gene homolog overlaps two genes in the antisense orientation on chromosome 1q.12. Endocrinology 2003, 144, 423–436. [Google Scholar] [CrossRef] [PubMed]
- van Biljon, W.; Wykes, S.; Scherer, S.; Krawetz, S.A.; Hapgood, J. Type II gonadotropin-releasing hormone receptor transcripts in human sperm. Biol. Reprod. 2002, 67, 1741–1749. [Google Scholar] [CrossRef] [Green Version]
- Grundker, C.; Schlotawa, L.; Viereck, V.; Eicke, N.; Horst, A.; Kairies, B.; Emons, G. Antiproliferative effects of the GnRH antagonist cetrorelix and of GnRH-II on human endometrial and ovarian cancer cells are not mediated through the GnRH type I receptor. Eur. J. Endocrinol. 2004, 151, 141–149. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Montagnani Marelli, M.; Moretti, R.M.; Mai, S.; Januszkiewicz-Caulier, J.; Motta, M.; Limonta, P. Type I gonadotropin-releasing hormone receptor mediates the antiproliferative effects of GnRH-II on prostate cancer cells. J. Clin. Endocrinol. Metab. 2009, 94, 1761–1767. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, K.Y.; Choi, K.C.; Auersperg, N.; Leung, P.C. Mechanism of gonadotropin-releasing hormone (GnRH)-I and -II-induced cell growth inhibition in ovarian cancer cells: Role of the GnRH-I receptor and protein kinase C pathway. Endocr. Relat. Cancer 2006, 13, 211–220. [Google Scholar] [CrossRef]
- Montagnani Marelli, M.; Moretti, R.M.; Dondi, D.; Limonta, P.; Motta, M. Effects of LHRH agonists on the growth of human prostatic tumor cells: “in vitro” and “in vivo” studies. Arch. Ital. Urol. Androl. 1997, 69, 257–263. [Google Scholar]
- Dondi, D.; Moretti, R.M.; Montagnani Marelli, M.; Pratesi, G.; Polizzi, D.; Milani, M.; Motta, M.; Limonta, P. Growth-inhibitory effects of luteinizing hormone-releasing hormone (LHRH) agonists on xenografts of the DU 145 human androgen-independent prostate cancer cell line in nude mice. Int. J. Cancer 1998, 76, 506–511. [Google Scholar] [CrossRef]
- Castellon, E.; Clementi, M.; Hitschfeld, C.; Sanchez, C.; Benitez, D.; Saenz, L.; Contreras, H.; Huidobro, C. Effect of leuprolide and cetrorelix on cell growth, apoptosis, and GnRH receptor expression in primary cell cultures from human prostate carcinoma. Cancer Investig. 2006, 24, 261–268. [Google Scholar] [CrossRef]
- Sundaram, S.; Durairaj, C.; Kadam, R.; Kompella, U.B. Luteinizing hormone-releasing hormone receptor-targeted deslorelin-docetaxel conjugate enhances efficacy of docetaxel in prostate cancer therapy. Mol. Cancer Ther. 2009, 8, 1655–1665. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Morgan, K.; Stavrou, E.; Leighton, S.P.; Miller, N.; Sellar, R.; Millar, R.P. Elevated GnRH receptor expression plus GnRH agonist treatment inhibits the growth of a subset of papillomavirus 18-immortalized human prostate cells. Prostate 2011, 71, 915–928. [Google Scholar] [CrossRef] [PubMed]
- Gnanapragasam, V.J.; Darby, S.; Khan, M.M.; Lock, W.G.; Robson, C.N.; Leung, H.Y. Evidence that prostate gonadotropin-releasing hormone receptors mediate an anti-tumourigenic response to analogue therapy in hormone refractory prostate cancer. J. Pathol. 2005, 206, 205–213. [Google Scholar] [CrossRef] [PubMed]
- Ben-Ami, I.; Yao, Z.; Naor, Z.; Seger, R. Gq protein-induced apoptosis is mediated by AKT kinase inhibition that leads to protein kinase C-induced c-Jun N-terminal kinase activation. J. Biol. Chem. 2011, 286, 31022–31031. [Google Scholar] [CrossRef] [Green Version]
- Nadel, G.; Yao, Z.; Ben-Ami, I.; Naor, Z.; Seger, R. Gq-Induced Apoptosis is Mediated by AKT Inhibition That Leads to PKC-Induced JNK Activation. Cell Physiol. Biochem. 2018, 50, 121–135. [Google Scholar] [CrossRef]
- Kraus, S.; Levy, G.; Hanoch, T.; Naor, Z.; Seger, R. Gonadotropin-releasing hormone induces apoptosis of prostate cancer cells: Role of c-Jun NH2-terminal kinase, protein kinase B, and extracellular signal-regulated kinase pathways. Cancer Res. 2004, 64, 5736–5744. [Google Scholar] [CrossRef] [Green Version]
- Kraus, S.; Naor, Z.; Seger, R. Gonadotropin-releasing hormone in apoptosis of prostate cancer cells. Cancer Lett. 2006, 234, 109–123. [Google Scholar] [CrossRef] [PubMed]
- Moretti, R.M.; Marelli, M.M.; Taylor, D.M.; Martini, P.G.V.; Marzagalli, M.; Limonta, P. Gonadotropin-Releasing Hormone Agonists Sensitize, and Resensitize, Prostate Cancer Cells to Docetaxel in a p53-Dependent Manner. PLoS ONE 2014, 9, e93713. [Google Scholar] [CrossRef]
- Clementi, M.; Sanchez, C.; Benitez, D.A.; Contreras, H.R.; Huidobro, C.; Cabezas, J.; Acevedo, C.; Castellon, E.A. Gonadotropin releasing hormone analogs induce apoptosis by extrinsic pathway involving p53 phosphorylation in primary cell cultures of human prostatic adenocarcinomas. Prostate 2009, 69, 1025–1033. [Google Scholar] [CrossRef]
- Sanchez, C.A.; Mercado, A.J.; Contreras, H.R.; Cabezas, J.C.; Huidobro, C.C.; Castellon, E.A. Pharmacoperone IN3 enhances the apoptotic effect of leuprolide in prostate cancer cells by increasing the gonadotropin-releasing hormone receptor in the cell membrane. Anticancer Drugs 2012, 23, 959–969. [Google Scholar] [CrossRef]
- Sviridonov, L.; Dobkin-Bekman, M.; Shterntal, B.; Przedecki, F.; Formishell, L.; Kravchook, S.; Rahamim-Ben Navi, L.; Bar-Lev, T.H.; Kazanietz, M.G.; Yao, Z.; et al. Differential signaling of the GnRH receptor in pituitary gonadotrope cell lines and prostate cancer cell lines. Mol. Cell. Endocrinol. 2013, 369, 107–118. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Limonta, P.; Moretti, R.M.; Dondi, D.; Marelli, M.M.; Motta, M. The EGF/TGFalpha system as an autocrine growth stimulatory loop in LNCaP cells. Endocr. Relat. Cancer 1994, 1, 5–13. [Google Scholar]
- Motta, M.; Dondi, D.; Moretti, R.M.; Marelli, M.M.; Pimpinelli, F.; Maggi, R.; Limonta, P. Role of growth factors, steroid and peptide hormones in the regulation of human prostatic tumor growth. J. Steroid Biochem. Mol. Biol. 1996, 56, 107–111. [Google Scholar] [CrossRef]
- Krueckl, S.L.; Sikes, R.A.; Edlund, N.M.; Bell, R.H.; Hurtado-Coll, A.; Fazli, L.; Gleave, M.E.; Cox, M.E. Increased insulin-like growth factor I receptor expression and signaling are components of androgen-independent progression in a lineage-derived prostate cancer progression model. Cancer 2004, 64, 8620–8629. [Google Scholar] [CrossRef] [Green Version]
- Lee, C.; Jia, Z.; Rahmatpanah, F.; Zhang, Q.; Zi, X.; McClelland, M.; Mercola, D. Role of the adjacent stroma cells in prostate cancer development and progression: Synergy between TGF-beta and IGF signaling. Biomed. Res. Int. 2014, 2014, 502093. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Biernacka, K.M.; Perks, C.M.; Holly, J.M. Role of the IGF axis in prostate cancer. Minerva Endocrinol. 2012, 37, 173–185. [Google Scholar] [PubMed]
- Wu, J.; Yu, E. Insulin-like growth factor receptor-1 (IGF-IR) as a target for prostate cancer therapy. Cancer Metastasis Rev. 2014, 33, 607–617. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Msaouel, P.; Galeas, J.N.; Boiles, A.R.; Ruiz, R.R.; Koutsilieris, M. Targeting the Bone Microenvironment in Metastatic Castration-Resistant Prostate Cancer. Curr. Drug Targets 2016, 17, 276–289. [Google Scholar] [CrossRef] [PubMed]
- Qu, X.; Wu, Z.; Dong, W.; Zhang, T.; Wang, L.; Pang, Z.; Ma, W.; Du, J. Update of IGF-1 receptor inhibitor (ganitumab, dalotuzumab, cixutumumab, teprotumumab and figitumumab) effects on cancer therapy. Oncotarget 2017, 8, 29501–29518. [Google Scholar] [CrossRef] [Green Version]
- Ahearn, T.U.; Peisch, S.; Pettersson, A.; Ebot, E.M.; Zhou, C.K.; Graff, R.E.; Sinnott, J.A.; Fazli, L.; Judson, G.L.; Bismar, T.A.; et al. Expression of IGF/insulin receptor in prostate cancer tissue and progression to lethal disease. Carcinogenesis 2018, 39, 1431–1437. [Google Scholar] [CrossRef] [PubMed]
- Mita, K.; Nakahara, M.; Usui, T. Expression of the insulin-like growth factor system and cancer progression in hormone-treated prostate cancer patients. Int. J. Urol. 2000, 7, 321–329. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Joshi, G.; Singh, P.K.; Negi, A.; Rana, A.; Singh, S.; Kumar, R. Growth factors mediated cell signalling in prostate cancer progression: Implications in discovery of anti-prostate cancer agents. Chem. Biol. Interact. 2015, 240, 120–133. [Google Scholar] [CrossRef] [PubMed]
- Montanari, M.; Rossetti, S.; Cavaliere, C.; D’Aniello, C.; Malzone, M.G.; Vanacore, D.; Di Franco, R.; La Mantia, E.; Iovane, G.; Piscitelli, R.; et al. Epithelial-mesenchymal transition in prostate cancer: An overview. Oncotarget 2017, 8, 35376–35389. [Google Scholar] [CrossRef] [Green Version]
- Culig, Z. Epithelial mesenchymal transition and resistance in endocrine-related cancers. Biochim. Biophys. Acta Mol. Cell Res. 2019, 1866, 1368–1375. [Google Scholar] [CrossRef]
- Moretti, R.M.; Marelli, M.M.; Dondi, D.; Poletti, A.; Martini, L.; Motta, M.; Limonta, P. Luteinizing hormone-releasing hormone agonists interfere with the stimulatory actions of epidermal growth factor in human prostatic cancer cell lines, LNCaP and DU 145. J. Clin. Endocrinol. Metab. 1996, 81, 3930–3937. [Google Scholar]
- Emons, G.; Muller, V.; Ortmann, O.; Schulz, K.D. Effects of LHRH-analogues on mitogenic signal transduction in cancer cells. J. Steroid Biochem. Mol. Biol. 1998, 65, 199–206. [Google Scholar] [CrossRef]
- Wells, A.; Souto, J.C.; Solava, J.; Kassis, J.; Bailey, K.J.; Turner, T. Luteinizing hormone-releasing hormone agonist limits DU-145 prostate cancer growth by attenuating epidermal growth factor receptor signaling. Clin. Cancer Res. 2002, 8, 1251–1257. [Google Scholar] [PubMed]
- Iacopino, F.; Lama, G.; Angelucci, C.; Sica, G. Leuprorelin acetate affects ERK1/2 activity in prostate cancer cells. Int. J. Oncol. 2006, 29, 237–247. [Google Scholar] [CrossRef] [PubMed]
- Jungwirth, A.; Pinski, J.; Galvan, G.; Halmos, G.; Szepeshazi, K.; Cai, R.Z.; Groot, K.; Vadillo-Buenfil, M.; Schally, A.V. Inhibition of growth of androgen-independent DU-145 prostate cancer in vivo by luteinising hormone-releasing hormone antagonist Cetrorelix and bombesin antagonists RC-3940-II and RC-3950-II. Eur. J. Cancer 1997, 33, 1141–1148. [Google Scholar] [CrossRef]
- Lamharzi, N.; Halmos, G.; Jungwirth, A.; Schally, A.V. Decrease in the level and mRNA expression of LH-RH and EGF receptors after treatment with LH-RH antagonist cetrorelix in DU-145 prostate tumor xenografts in nude mice. Int. J. Oncol. 1998, 13, 429–435. [Google Scholar] [CrossRef] [Green Version]
- Mezo, G.; Manea, M. Luteinizing hormone-releasing hormone antagonists. Expert Opin. Ther. Pat. 2009, 19, 1771–1785. [Google Scholar] [CrossRef] [Green Version]
- Sakai, M.; Martinez-Arguelles, D.B.; Patterson, N.H.; Chaurand, P.; Papadopoulos, V. In search of the molecular mechanisms mediating the inhibitory effect of the GnRH antagonist degarelix on human prostate cell growth. PLoS ONE 2015, 10, e0120670. [Google Scholar] [CrossRef] [PubMed]
- Cucchiara, V.; Yang, J.C.; Liu, C.; Adomat, H.H.; Tomlinson Guns, E.S.; Gleave, M.E.; Gao, A.C.; Evans, C.P. GnRH Antagonists Have Direct Inhibitory Effects on Castration-Resistant Prostate Cancer Via Intracrine Androgen and AR-V7 Expression. Mol. Cancer Ther. 2019, 18, 1811–1821. [Google Scholar] [CrossRef] [Green Version]
- Liu, C.; Lou, W.; Yang, J.C.; Liu, L.; Armstrong, C.M.; Lombard, A.P.; Zhao, R.; Noel, O.D.V.; Tepper, C.G.; Chen, H.W.; et al. Proteostasis by STUB1/HSP70 complex controls sensitivity to androgen receptor targeted therapy in advanced prostate cancer. Nat. Commun. 2018, 9, 4700. [Google Scholar] [CrossRef]
- Moses, M.A.; Kim, Y.S.; Rivera-Marquez, G.M.; Oshima, N.; Watson, M.J.; Beebe, K.E.; Wells, C.; Lee, S.; Zuehlke, A.D.; Shao, H.; et al. Targeting the Hsp40/Hsp70 Chaperone Axis as a Novel Strategy to Treat Castration-Resistant Prostate Cancer. Cancer Res. 2018, 78, 4022–4035. [Google Scholar] [CrossRef] [Green Version]
- Liu, L.L.; Xie, N.; Sun, S.; Plymate, S.; Mostaghel, E.; Dong, X. Mechanisms of the androgen receptor splicing in prostate cancer cells. Oncogene 2014, 33, 3140–3150. [Google Scholar] [CrossRef] [Green Version]
- Tummala, R.; Lou, W.; Gao, A.C.; Nadiminty, N. Quercetin Targets hnRNPA1 to Overcome Enzalutamide Resistance in Prostate Cancer Cells. Mol. Cancer Ther. 2017, 16, 2770–2779. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, Z.; Wu, D.; Thomas-Ahner, J.M.; Lu, C.; Zhao, P.; Zhang, Q.; Geraghty, C.; Yan, P.S.; Hankey, W.; Sunkel, B.; et al. Diverse AR-V7 cistromes in castration-resistant prostate cancer are governed by HoxB13. Proc. Natl. Acad. Sci. USA 2018, 115, 6810–6815. [Google Scholar] [CrossRef] [Green Version]
- Fan, L.; Zhang, F.; Xu, S.; Cui, X.; Hussain, A.; Fazli, L.; Gleave, M.; Dong, X.; Qi, J. Histone demethylase JMJD1A promotes alternative splicing of AR variant 7 (AR-V7) in prostate cancer cells. Proc. Natl. Acad. Sci. USA 2018, 115, E4584–E4593. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Millar, R.P.; Pawson, A.J.; Morgan, K.; Rissman, E.F.; Lu, Z.L. Diversity of actions of GnRHs mediated by ligand-induced selective signaling. Front. Neuroendocrinol. 2008, 29, 17–35. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Darby, S.; Stockley, J.; Khan, M.M.; Robson, C.N.; Leung, H.Y.; Gnanapragasam, V.J. Expression of GnRH type II is regulated by the androgen receptor in prostate cancer. Endocr. Relat. Cancer 2007, 14, 613–624. [Google Scholar] [CrossRef] [Green Version]
- Maiti, K.; Oh, D.Y.; Moon, J.S.; Acharjee, S.; Li, J.H.; Bai, D.G.; Park, H.S.; Lee, K.; Lee, Y.C.; Jung, N.C.; et al. Differential effects of gonadotropin-releasing hormone (GnRH)-I and GnRH-II on prostate cancer cell signaling and death. J. Clin. Endocrinol. Metab. 2005, 90, 4287–4298. [Google Scholar] [CrossRef] [Green Version]
- Pezaro, C.; Omlin, A.; Lorente, D.; Rodrigues, D.N.; Ferraldeschi, R.; Bianchini, D.; Mukherji, D.; Riisnaes, R.; Altavilla, A.; Crespo, M.; et al. Visceral disease in castration-resistant prostate cancer. Eur. Urol. 2014, 65, 270–273. [Google Scholar] [CrossRef] [Green Version]
- Den, R.B.; George, D.; Pieczonka, C.; McNamara, M. Ra-223 Treatment for Bone Metastases in Castrate-Resistant Prostate Cancer: Practical Management Issues for Patient Selection. Am. J. Clin. Oncol. 2019, 42, 399–406. [Google Scholar] [CrossRef]
- Conteduca, V.; Mosca, A.; Brighi, N.; de Giorgi, U.; Rescigno, P. New Prognostic Biomarkers in Metastatic Castration-Resistant Prostate Cancer. Cells 2021, 10, 193. [Google Scholar] [CrossRef] [PubMed]
- Mollica, V.; Rizzo, A.; Rosellini, M.; Marchetti, A.; Ricci, A.D.; Cimadamore, A.; Scarpelli, M.; Bonucci, C.; Andrini, E.; Errani, C.; et al. Bone Targeting Agents in Patients with Metastatic Prostate Cancer: State of the Art. Cancers 2021, 13, 546. [Google Scholar] [CrossRef]
- Montagnani Marelli, M.; Moretti, R.M.; Mai, S.; Procacci, P.; Limonta, P. Gonadotropin-releasing hormone agonists reduce the migratory and the invasive behavior of androgen-independent prostate cancer cells by interfering with the activity of IGF-I. Int. J. Oncol. 2007, 30, 261–271. [Google Scholar] [CrossRef] [Green Version]
- Enomoto, M.; Utsumi, M.; Park, M.K. Gonadotropin-releasing hormone induces actin cytoskeleton remodeling and affects cell migration in a cell-type-specific manner in TSU-Pr1 and DU145 cells. Endocrinology 2006, 147, 530–542. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Dondi, D.; Festuccia, C.; Piccolella, M.; Bologna, M.; Motta, M. GnRH agonists and antagonists decrease the metastatic progression of human prostate cancer cell lines by inhibiting the plasminogen activator system. Oncol. Rep. 2006, 15, 393–400. [Google Scholar] [CrossRef] [Green Version]
- Yates, C.; Wells, A.; Turner, T. Luteinising hormone-releasing hormone analogue reverses the cell adhesion profile of EGFR overexpressing DU-145 human prostate carcinoma subline. Br. J. Cancer 2005, 92, 366–375. [Google Scholar] [CrossRef] [Green Version]
- Marzagalli, M.; Fontana, F.; Raimondi, M.; Limonta, P. Cancer Stem Cells-Key Players in Tumor Relapse. Cancers 2021, 13, 376. [Google Scholar] [CrossRef]
- Castillo, V.; Valenzuela, R.; Huidobro, C.; Contreras, H.R.; Castellon, E.A. Functional characteristics of cancer stem cells and their role in drug resistance of prostate cancer. Int. J. Oncol. 2014, 45, 985–994. [Google Scholar] [CrossRef] [PubMed]
- Hanahan, D.; Weinberg, R.A. Hallmarks of cancer: The next generation. Cell 2011, 144, 646–674. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mukwaya, A.; Jensen, L.; Lagali, N. Relapse of pathological angiogenesis: Functional role of the basement membrane and potential treatment strategies. Exp. Mol. Med. 2021, 53, 189–201. [Google Scholar] [CrossRef] [PubMed]
- Rajabi, M.; Mousa, S.A. The Role of Angiogenesis in Cancer Treatment. Biomedicines 2017, 5, 34. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Chen, Y.; Zhang, L.; Liu, W.X.; Wang, K. VEGF and SEMA4D have synergistic effects on the promotion of angiogenesis in epithelial ovarian cancer. Cell. Mol. Biol. Lett. 2018, 23, 2. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Lopez, A.; Harada, K.; Vasilakopoulou, M.; Shanbhag, N.; Ajani, J.A. Targeting Angiogenesis in Colorectal Carcinoma. Drugs 2019, 79, 63–74. [Google Scholar] [CrossRef] [PubMed]
- Madu, C.O.; Wang, S.; Madu, C.O.; Lu, Y. Angiogenesis in Breast Cancer Progression, Diagnosis, and Treatment. J. Cancer 2020, 11, 4474–4494. [Google Scholar] [CrossRef]
- Tian, W.; Cao, C.; Shu, L.; Wu, F. Anti-Angiogenic Therapy in the Treatment of Non-Small Cell Lung Cancer. OncoTargets Ther. 2020, 13, 12113–12129. [Google Scholar] [CrossRef]
- Ghafouri, S.; Burkenroad, A.; Pantuck, M.; Almomani, B.; Stefanoudakis, D.; Shen, J.; Drakaki, A. VEGF inhibition in urothelial cancer: The past, present and future. World J. Urol. 2021, 39, 741–749. [Google Scholar] [CrossRef] [PubMed]
- Wong, S.Y.; Haack, H.; Crowley, D.; Barry, M.; Bronson, R.T.; Hynes, R.O. Tumor-secreted vascular endothelial growth factor-C is necessary for prostate cancer lymphangiogenesis, but lymphangiogenesis is unnecessary for lymph node metastasis. Cancer Res. 2005, 65, 9789–9798. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Melegh, Z.; Oltean, S. Targeting Angiogenesis in Prostate Cancer. Int. J. Mol. Sci. 2019, 20, 2676. [Google Scholar] [CrossRef] [Green Version]
- Sarkar, C.; Goswami, S.; Basu, S.; Chakroborty, D. Angiogenesis Inhibition in Prostate Cancer: An Update. Cancers 2020, 12, 2382. [Google Scholar] [CrossRef] [PubMed]
- Hrouda, D.; Nicol, D.L.; Gardiner, R.A. The role of angiogenesis in prostate development and the pathogenesis of prostate cancer. Urol. Res. 2003, 30, 347–355. [Google Scholar] [CrossRef] [PubMed]
- Green, M.M.; Hiley, C.T.; Shanks, J.H.; Bottomley, I.C.; West, C.M.; Cowan, R.A.; Stratford, I.J. Expression of vascular endothelial growth factor (VEGF) in locally invasive prostate cancer is prognostic for radiotherapy outcome. Int. J. Radiat. Oncol. Biol. Phys. 2007, 67, 84–90. [Google Scholar] [CrossRef] [PubMed]
- Moretti, R.M.; Mai, S.; Montagnani Marelli, M.; Bani, M.R.; Ghilardi, C.; Giavazzi, R.; Taylor, D.M.; Martini, P.G.; Limonta, P. Dual targeting of tumor and endothelial cells by gonadotropin-releasing hormone agonists to reduce melanoma angiogenesis. Endocrinology 2010, 151, 4643–4653. [Google Scholar] [CrossRef] [Green Version]
- Li, M.; Xu, H.; Wang, J. Optimized functional and structural design of dual-target LMRAP, a bifunctional fusion protein with a 25-amino-acid antitumor peptide and GnRH Fc fragment. Acta Pharm. Sin. B 2020, 10, 262–275. [Google Scholar] [CrossRef] [PubMed]
- Imai, A.; Tamaya, T. GnRH receptor and apoptotic signaling. Vitam. Horm. 2000, 59, 1–33. [Google Scholar]
- Maudsley, S.; Davidson, L.; Pawson, A.J.; Chan, R.; Lopez de Maturana, R.; Millar, R.P. Gonadotropin-releasing hormone (GnRH) antagonists promote proapoptotic signaling in peripheral reproductive tumor cells by activating a Galphai-coupling state of the type I GnRH receptor. Cancer Res. 2004, 64, 7533–7544. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Grundker, C.; Volker, P.; Emons, G. Antiproliferative signaling of luteinizing hormone-releasing hormone in human endometrial and ovarian cancer cells through G protein alpha(I)-mediated activation of phosphotyrosine phosphatase. Endocrinology 2001, 142, 2369–2380. [Google Scholar] [CrossRef]
- Fister, S.; Gunthert, A.R.; Aicher, B.; Paulini, K.W.; Emons, G.; Grundker, C. GnRH-II antagonists induce apoptosis in human endometrial, ovarian, and breast cancer cells via activation of stress-induced MAPKs p38 and JNK and proapoptotic protein Bax. Cancer Res. 2009, 69, 6473–6481. [Google Scholar] [CrossRef] [Green Version]
- Naor, Z. Signaling by G-protein-coupled receptor (GPCR): Studies on the GnRH receptor. Front. Neuroendocrinol. 2009, 30, 10–29. [Google Scholar] [CrossRef] [PubMed]
- James, N.D.; Sydes, M.R.; Clarke, N.W.; Mason, M.D.; Dearnaley, D.P.; Spears, M.R.; Ritchie, A.W.; Parker, C.C.; Russell, J.M.; Attard, G.; et al. Addition of docetaxel, zoledronic acid, or both to first-line long-term hormone therapy in prostate cancer (STAMPEDE): Survival results from an adaptive, multiarm, multistage, platform randomised controlled trial. Lancet 2016, 387, 1163–1177. [Google Scholar] [CrossRef] [Green Version]
- Fizazi, K.; Tran, N.; Fein, L.; Matsubara, N.; Rodriguez-Antolin, A.; Alekseev, B.Y.; Ozguroglu, M.; Ye, D.; Feyerabend, S.; Protheroe, A.; et al. Abiraterone plus Prednisone in Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. 2017, 377, 352–360. [Google Scholar] [CrossRef] [PubMed]
- James, N.D.; de Bono, J.S.; Spears, M.R.; Clarke, N.W.; Mason, M.D.; Dearnaley, D.P.; Ritchie, A.W.S.; Amos, C.L.; Gilson, C.; Jones, R.J.; et al. Abiraterone for Prostate Cancer Not Previously Treated with Hormone Therapy. N. Engl. J. Med. 2017, 377, 338–351. [Google Scholar] [CrossRef] [PubMed]
- Armstrong, A.J.; Szmulewitz, R.Z.; Petrylak, D.P.; Holzbeierlein, J.; Villers, A.; Azad, A.; Alcaraz, A.; Alekseev, B.; Iguchi, T.; Shore, N.D.; et al. ARCHES: A Randomized, Phase III Study of Androgen Deprivation Therapy with Enzalutamide or Placebo in Men with Metastatic Hormone-Sensitive Prostate Cancer. J. Clin. Oncol. 2019, 37, 2974–2986. [Google Scholar] [CrossRef] [PubMed]
- Chi, K.N.; Agarwal, N.; Bjartell, A.; Chung, B.H.; Pereira de Santana Gomes, A.J.; Given, R.; Juarez Soto, A.; Merseburger, A.S.; Ozguroglu, M.; Uemura, H.; et al. Apalutamide for Metastatic, Castration-Sensitive Prostate Cancer. N. Engl. J. Med. 2019, 381, 13–24. [Google Scholar] [CrossRef]
- Davis, I.D.; Martin, A.J.; Stockler, M.R.; Begbie, S.; Chi, K.N.; Chowdhury, S.; Coskinas, X.; Frydenberg, M.; Hague, W.E.; Horvath, L.G.; et al. Enzalutamide with Standard First-Line Therapy in Metastatic Prostate Cancer. N. Engl. J. Med. 2019, 381, 121–131. [Google Scholar] [CrossRef] [PubMed]
- Kim, T.J.; Lee, Y.H.; Koo, K.C. Current Status and Future Perspectives of Androgen Receptor Inhibition Therapy for Prostate Cancer: A Comprehensive Review. Biomolecules 2021, 11, 492. [Google Scholar] [CrossRef] [PubMed]
- Hernando Polo, S.; Moreno Munoz, D.; Rosero Rodriguez, A.C.; Silva Ruiz, J.; Rosero Rodriguez, D.I.; Counago, F. Changing the History of Prostate Cancer with New Targeted Therapies. Biomedicines 2021, 9, 392. [Google Scholar] [CrossRef] [PubMed]
- Oudard, S.; Fizazi, K.; Sengelov, L.; Daugaard, G.; Saad, F.; Hansen, S.; Hjalm-Eriksson, M.; Jassem, J.; Thiery-Vuillemin, A.; Caffo, O.; et al. Cabazitaxel Versus Docetaxel as First-Line Therapy for Patients with Metastatic Castration-Resistant Prostate Cancer: A Randomized Phase III Trial-FIRSTANA. J. Clin. Oncol. 2017, 35, 3189–3197. [Google Scholar] [CrossRef]
- Antonarakis, E.S.; Piulats, J.M.; Gross-Goupil, M.; Goh, J.; Ojamaa, K.; Hoimes, C.J.; Vaishampayan, U.; Berger, R.; Sezer, A.; Alanko, T.; et al. Pembrolizumab for Treatment-Refractory Metastatic Castration-Resistant Prostate Cancer: Multicohort, Open-Label Phase II KEYNOTE-199 Study. J. Clin. Oncol. 2020, 38, 395–405. [Google Scholar] [CrossRef]
- Hawsawi, Y.M.; Zailaie, S.A.; Oyouni, A.A.A.; Alzahrani, O.R.; Alamer, O.M.; Aljohani, S.A.S. Prostate cancer and therapeutic challenges. J. Biol. Res. 2020, 27, 20. [Google Scholar]
- Shore, N.D.; Drake, C.G.; Lin, D.W.; Ryan, C.J.; Stratton, K.L.; Dunshee, C.; Karsh, L.I.; Kaul, S.; Kernen, K.; Pieczonka, C.; et al. Optimizing the management of castration-resistant prostate cancer patients: A practical guide for clinicians. Prostate 2020, 80, 1159–1176. [Google Scholar] [CrossRef]
- Bansal, D.; Reimers, M.A.; Knoche, E.M.; Pachynski, R.K. Immunotherapy and Immunotherapy Combinations in Metastatic Castration-Resistant Prostate Cancer. Cancers 2021, 13, 334. [Google Scholar] [CrossRef] [PubMed]
- Rebello, R.J.; Oing, C.; Knudsen, K.E.; Loeb, S.; Johnson, D.C.; Reiter, R.E.; Gillessen, S.; Van der Kwast, T.; Bristow, R.G. Prostate cancer. Nature Rev. Dis. Primers 2021, 7, 9. [Google Scholar] [CrossRef]
- Desai, K.; McManus, J.; Sharifi, N. Hormonal Therapy for Prostate Cancer. Endocr. Rev. 2021, bnab002. [Google Scholar] [CrossRef]
- Scher, H.I.; Fizazi, K.; Saad, F.; Taplin, M.E.; Sternberg, C.N.; Miller, K.; de Wit, R.; Mulders, P.; Chi, K.N.; Shore, N.D.; et al. Increased survival with enzalutamide in prostate cancer after chemotherapy. N. Engl. J. Med. 2012, 367, 1187–1197. [Google Scholar] [CrossRef] [Green Version]
- Beer, T.M.; Armstrong, A.J.; Rathkopf, D.E.; Loriot, Y.; Sternberg, C.N.; Higano, C.S.; Iversen, P.; Bhattacharya, S.; Carles, J.; Chowdhury, S.; et al. Enzalutamide in metastatic prostate cancer before chemotherapy. N. Engl. J. Med. 2014, 371, 424–433. [Google Scholar] [CrossRef] [Green Version]
- Penson, D.F.; Armstrong, A.J.; Concepcion, R.; Agarwal, N.; Olsson, C.; Karsh, L.; Dunshee, C.; Wang, F.; Wu, K.; Krivoshik, A.; et al. Enzalutamide Versus Bicalutamide in Castration-Resistant Prostate Cancer: The STRIVE Trial. J. Clin. Oncol. 2016, 34, 2098–2106. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hussain, M.; Fizazi, K.; Saad, F.; Rathenborg, P.; Shore, N.; Ferreira, U.; Ivashchenko, P.; Demirhan, E.; Modelska, K.; Phung, D.; et al. Enzalutamide in Men with Nonmetastatic, Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2018, 378, 2465–2474. [Google Scholar] [CrossRef]
- Smith, M.R.; Antonarakis, E.S.; Ryan, C.J.; Berry, W.R.; Shore, N.D.; Liu, G.; Alumkal, J.J.; Higano, C.S.; Chow Maneval, E.; Bandekar, R.; et al. Phase 2 Study of the Safety and Antitumor Activity of Apalutamide (ARN-509), a Potent Androgen Receptor Antagonist, in the High-risk Nonmetastatic Castration-resistant Prostate Cancer Cohort. Eur. Urol. 2016, 70, 963–970. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Saad, F.; Cella, D.; Basch, E.; Hadaschik, B.A.; Mainwaring, P.N.; Oudard, S.; Graff, J.N.; McQuarrie, K.; Li, S.; Hudgens, S.; et al. Effect of apalutamide on health-related quality of life in patients with non-metastatic castration-resistant prostate cancer: An analysis of the SPARTAN randomised, placebo-controlled, phase 3 trial. Lancet Oncol. 2018, 19, 1404–1416. [Google Scholar] [CrossRef]
- Fizazi, K.; Smith, M.R.; Tombal, B. Clinical Development of Darolutamide: A Novel Androgen Receptor Antagonist for the Treatment of Prostate Cancer. Clin. Genitourin. Cancer 2018, 16, 332–340. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- de Bono, J.S.; Logothetis, C.J.; Molina, A.; Fizazi, K.; North, S.; Chu, L.; Chi, K.N.; Jones, R.J.; Goodman, O.B., Jr.; Saad, F.; et al. Abiraterone and increased survival in metastatic prostate cancer. N. Engl. J. Med. 2011, 364, 1995–2005. [Google Scholar] [CrossRef]
- Ryan, C.J.; Smith, M.R.; de Bono, J.S.; Molina, A.; Logothetis, C.J.; de Souza, P.; Fizazi, K.; Mainwaring, P.; Piulats, J.M.; Ng, S.; et al. Abiraterone in metastatic prostate cancer without previous chemotherapy. N. Engl. J. Med. 2013, 368, 138–148. [Google Scholar] [CrossRef] [Green Version]
- Ryan, C.J.; Smith, M.R.; Fizazi, K.; Saad, F.; Mulders, P.F.; Sternberg, C.N.; Miller, K.; Logothetis, C.J.; Shore, N.D.; Small, E.J.; et al. Abiraterone acetate plus prednisone versus placebo plus prednisone in chemotherapy-naive men with metastatic castration-resistant prostate cancer (COU-AA-302): Final overall survival analysis of a randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol. 2015, 16, 152–160. [Google Scholar] [CrossRef]
- Fallara, G.; Lissbrant, I.F.; Styrke, J.; Montorsi, F.; Garmo, H.; Stattin, P. Observational study on time on treatment with abiraterone and enzalutamide. PLoS ONE 2020, 15, e0244462. [Google Scholar] [CrossRef]
- Lawrentschuk, N.; Fernandes, K.; Bell, D.; Barkin, J.; Fleshner, N. Efficacy of a second line luteinizing hormone-releasing hormone agonist after advanced prostate cancer biochemical recurrence. J. Urol. 2011, 185, 848–854. [Google Scholar] [CrossRef] [PubMed]
- Jang, H.S.; Koo, K.C.; Cho, K.S.; Chung, B.H. Survival Outcomes of Concurrent Treatment with Docetaxel and Androgen Deprivation Therapy in Metastatic Castration-Resistant Prostate Cancer. Yonsei Med. J. 2016, 57, 1070–1078. [Google Scholar] [CrossRef]
- Merseburger, A.S.; Hupe, M.C. An Update on Triptorelin: Current Thinking on Androgen Deprivation Therapy for Prostate Cancer. Adv. Ther. 2016, 33, 1072–1093. [Google Scholar] [CrossRef] [Green Version]
- Tombal, B.; Cornel, E.B.; Persad, R.; Stari, A.; Gomez Veiga, F.; Schulman, C. Clinical Outcomes and Testosterone Levels Following Continuous Androgen Deprivation in Patients with Relapsing or Locally Advanced Prostate Cancer: A Post Hoc Analysis of the ICELAND Study. J. Urol. 2017, 198, 1054–1060. [Google Scholar] [CrossRef]
- Crawford, E.D.; Tombal, B.; Keane, T.; Boccardo, F.; Miller, K.; Shore, N.; Moul, J.W.; Damber, J.E.; Collette, L.; Persson, B.E. FSH suppression and tumour control in patients with prostate cancer during androgen deprivation with a GnRH agonist or antagonist. Scand. J. Urol. 2018, 52, 349–357. [Google Scholar] [CrossRef] [PubMed]
- Klotz, L.; Boccon-Gibod, L.; Shore, N.D.; Andreou, C.; Persson, B.E.; Cantor, P.; Jensen, J.K.; Olesen, T.K.; Schroder, F.H. The efficacy and safety of degarelix: A 12-month, comparative, randomized, open-label, parallel-group phase III study in patients with prostate cancer. BJU Int. 2008, 102, 1531–1538. [Google Scholar] [CrossRef]
- Tombal, B.; Miller, K.; Boccon-Gibod, L.; Schroder, F.; Shore, N.; Crawford, E.D.; Moul, J.; Jensen, J.K.; Kold Olesen, T.; Persson, B.E. Additional analysis of the secondary end point of biochemical recurrence rate in a phase 3 trial (CS21) comparing degarelix 80 mg versus leuprolide in prostate cancer patients segmented by baseline characteristics. Eur. Urol. 2010, 57, 836–842. [Google Scholar] [CrossRef] [PubMed]
- Clinton, T.N.; Woldu, S.L.; Raj, G.V. Degarelix versus luteinizing hormone-releasing hormone agonists for the treatment of prostate cancer. Expert Opin. Pharmacother. 2017, 18, 825–832. [Google Scholar] [CrossRef] [PubMed]
- Sugimura, R.; Kawahara, T.; Miyoshi, Y.; Yao, M.; Chiba, S.; Uemura, H. A Case of Switching from GnRH Agonist to Antagonist for Castration Resistant Prostate Cancer Control. Case Rep. Oncol. 2019, 12, 688–692. [Google Scholar] [CrossRef]
- Atchia, K.S.; Wallis, C.J.D.; Fleshner, N.; Toren, P. Switching from a gonadotropin-releasing hormone (GnRH) agonist to a GnRH antagonist in prostate cancer patients: A systematic review and meta-analysis. Can. Urol. Assoc. J. 2020, 14, 36–41. [Google Scholar]
- Kunath, F.; Borgmann, H.; Blumle, A.; Keck, B.; Wullich, B.; Schmucker, C.; Sikic, D.; Roelle, C.; Schmidt, S.; Wahba, A.; et al. Gonadotropin-releasing hormone antagonists versus standard androgen suppression therapy for advanced prostate cancer A systematic review with meta-analysis. BMJ Open 2015, 5, e008217. [Google Scholar] [CrossRef]
- Pham, T.; Sadowski, M.C.; Li, H.; Richard, D.J.; d’Emden, M.C.; Richard, K. Advances in hormonal therapies for hormone naive and castration-resistant prostate cancers with or without previous chemotherapy. Exp. Hematol. Oncol. 2015, 5, 15. [Google Scholar] [CrossRef] [Green Version]
- Schally, A.V.; Engel, J.B.; Emons, G.; Block, N.L.; Pinski, J. Use of analogs of peptide hormones conjugated to cytotoxic radicals for chemotherapy targeted to receptors on tumors. Curr. Drug Deliv. 2011, 8, 11–25. [Google Scholar] [CrossRef] [PubMed]
- Engel, J.B.; Tinneberg, H.R.; Rick, F.G.; Berkes, E.; Schally, A.V. Targeting of Peptide Cytotoxins to LHRH Receptors For Treatment of Cancer. Curr. Drug Targets 2016, 17, 488–494. [Google Scholar] [CrossRef] [PubMed]
- Fodor, K.; Dobos, N.; Schally, A.; Steiber, Z.; Olah, G.; Sipos, E.; Szekvolgyi, L.; Halmos, G. The targeted LHRH analog AEZS-108 alters expression of genes related to angiogenesis and development of metastasis in uveal melanoma. Oncotarget 2020, 11, 175–187. [Google Scholar] [CrossRef] [Green Version]
- Letsch, M.; Schally, A.V.; Szepeshazi, K.; Halmos, G.; Nagy, A. Preclinical evaluation of targeted cytotoxic luteinizing hormone-releasing hormone analogue AN-152 in androgen-sensitive and insensitive prostate cancers. Clin. Cancer Res. 2003, 9, 4505–4513. [Google Scholar]
- Engel, J.; Emons, G.; Pinski, J.; Schally, A.V. AEZS-108: A targeted cytotoxic analog of LHRH for the treatment of cancers positive for LHRH receptors. Expert Opin. Investig. Drugs 2012, 21, 891–899. [Google Scholar] [CrossRef] [PubMed]
- Popovics, P.; Schally, A.V.; Szalontay, L.; Block, N.L.; Rick, F.G. Targeted cytotoxic analog of luteinizing hormone-releasing hormone (LHRH), AEZS-108 (AN-152), inhibits the growth of DU-145 human castration-resistant prostate cancer in vivo and in vitro through elevating p21 and ROS levels. Oncotarget 2014, 5, 4567–4578. [Google Scholar] [CrossRef] [Green Version]
- Liu, S.V.; Tsao-Wei, D.D.; Xiong, S.; Groshen, S.; Dorff, T.B.; Quinn, D.I.; Tai, Y.C.; Engel, J.; Hawes, D.; Schally, A.V.; et al. Phase I, dose-escalation study of the targeted cytotoxic LHRH analog AEZS-108 in patients with castration- and taxane-resistant prostate cancer. Clin. Cancer Res. 2014, 20, 6277–6283. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Yu, S.S.; Athreya, K.; Liu, S.V.; Schally, A.V.; Tsao-Wei, D.; Groshen, S.; Quinn, D.I.; Dorff, T.B.; Xiong, S.; Engel, J.; et al. A Phase II Trial of AEZS-108 in Castration- and Taxane-Resistant Prostate Cancer. Clin. Genitourin. Cancer 2017, 15, 742–749. [Google Scholar] [CrossRef]
- Karampelas, T.; Argyros, O.; Sayyad, N.; Spyridaki, K.; Pappas, C.; Morgan, K.; Kolios, G.; Millar, R.P.; Liapakis, G.; Tzakos, A.G.; et al. GnRH-Gemcitabine conjugates for the treatment of androgen-independent prostate cancer: Pharmacokinetic enhancements combined with targeted drug delivery. Bioconjug. Chem. 2014, 25, 813–823. [Google Scholar] [CrossRef] [Green Version]
- Argyros, O.; Karampelas, T.; Asvos, X.; Varela, A.; Sayyad, N.; Papakyriakou, A.; Davos, C.H.; Tzakos, A.G.; Fokas, D.; Tamvakopoulos, C. Peptide-Drug Conjugate GnRH-Sunitinib Targets Angiogenesis Selectively at the Site of Action to Inhibit Tumor Growth. Cancer Res. 2016, 76, 1181–1192. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Marelli, M.M.; Manea, M.; Moretti, R.M.; Marzagalli, M.; Limonta, P. Oxime bond-linked daunorubicin-GnRH-III bioconjugates exert antitumor activity in castration-resistant prostate cancer cells via the type I GnRH receptor. Int. J. Oncol. 2015, 46, 243–253. [Google Scholar] [CrossRef]
- Rachner, T.D.; Tsourdi, E.; Hofbauer, L.C. Apalutamide and Metastasis-free Survival in Prostate Cancer. N. Engl. J. Med. 2018, 378, 2541–2542. [Google Scholar]
- Smith, M.R.; Saad, F.; Chowdhury, S.; Oudard, S.; Hadaschik, B.A.; Graff, J.N.; Olmos, D.; Mainwaring, P.N.; Lee, J.Y.; Uemura, H.; et al. Apalutamide Treatment and Metastasis-free Survival in Prostate Cancer. N. Engl. J. Med. 2018, 378, 1408–1418. [Google Scholar] [CrossRef]
- Fizazi, K.; Shore, N.; Tammela, T.L.; Ulys, A.; Vjaters, E.; Polyakov, S.; Jievaltas, M.; Luz, M.; Alekseev, B.; Kuss, I.; et al. Darolutamide in Nonmetastatic, Castration-Resistant Prostate Cancer. N. Engl. J. Med. 2019, 380, 1235–1246. [Google Scholar] [CrossRef]
- Small, E.J.; Saad, F.; Chowdhury, S.; Oudard, S.; Hadaschik, B.A.; Graff, J.N.; Olmos, D.; Mainwaring, P.N.; Lee, J.Y.; Uemura, H.; et al. Apalutamide and overall survival in non-metastatic castration-resistant prostate cancer. Ann. Oncol. 2019, 30, 1813–1820. [Google Scholar] [CrossRef] [Green Version]
- Beltran, H.; Romanel, A.; Conteduca, V.; Casiraghi, N.; Sigouros, M.; Franceschini, G.M.; Orlando, F.; Fedrizzi, T.; Ku, S.Y.; Dann, E.; et al. Circulating tumor DNA profile recognizes transformation to castration-resistant neuroendocrine prostate cancer. J. Clin. Investig. 2020, 130, 1653–1668. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Wu, Z.; Wang, K.; Yang, Z.; Pascal, L.E.; Nelson, J.B.; Takubo, K.; Wipf, P.; Wang, Z. A novel androgen receptor antagonist JJ-450 inhibits enzalutamide-resistant mutant AR(F876L) nuclear import and function. Prostate 2020, 80, 319–328. [Google Scholar] [CrossRef]
- Bhole, R.P.; Chikhale, R.V.; Wavhale, R.D.; Asmary, F.A.; Almutairi, T.M.; Alhajri, H.M.; Bonde, C.G. Design, synthesis and evaluation of novel enzalutamide analogues as potential anticancer agents. Heliyon 2021, 7, e06227. [Google Scholar] [CrossRef]
- Narayanan, R.; Ponnusamy, S.; Miller, D.D. Destroying the androgen receptor (AR)-potential strategy to treat advanced prostate cancer. Oncoscience 2017, 4, 175–177. [Google Scholar] [CrossRef] [PubMed]
- Merseburger, A.S.; Waldron, N.; Ribal, M.J.; Heidenreich, A.; Perner, S.; Fizazi, K.; Sternberg, C.N.; Mateo, J.; Wirth, M.P.; Castro, E.; et al. Genomic Testing in Patients with Metastatic Castration-resistant Prostate Cancer: A Pragmatic Guide for Clinicians. Eur. Urol. 2021, 79, 519–529. [Google Scholar] [CrossRef] [PubMed]
- Schmidt, K.T.; Huitema, A.D.R.; Chau, C.H.; Figg, W.D. Resistance to second-generation androgen receptor antagonists in prostate cancer. Nat. Rev. Urol. 2021, 18, 209–226. [Google Scholar] [CrossRef] [PubMed]
- Tai, Y.L.; Lin, C.J.; Li, T.K.; Shen, T.L.; Hsieh, J.T.; Chen, B.P.C. The role of extracellular vesicles in prostate cancer with clinical applications. Endocr. Relat. Cancer 2020, 27, R133–R144. [Google Scholar] [CrossRef] [PubMed]
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. |
© 2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
Share and Cite
Fontana, F.; Limonta, P. Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer. Cells 2021, 10, 1133. https://doi.org/10.3390/cells10051133
Fontana F, Limonta P. Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer. Cells. 2021; 10(5):1133. https://doi.org/10.3390/cells10051133
Chicago/Turabian StyleFontana, Fabrizio, and Patrizia Limonta. 2021. "Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer" Cells 10, no. 5: 1133. https://doi.org/10.3390/cells10051133
APA StyleFontana, F., & Limonta, P. (2021). Dissecting the Hormonal Signaling Landscape in Castration-Resistant Prostate Cancer. Cells, 10(5), 1133. https://doi.org/10.3390/cells10051133