Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer

Liu, Yifu; Fu, Shengqiang; Yan, Yuchang; Gong, Baoan; Xie, Wenjie; Yang, Xiaorong; Sun, Ting; Ma, Ming

doi:10.2147/dddt.s291369

Cited by 11 publications

(4 citation statements)

References 61 publications

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“…11 The development of LHRH agonists and GnRH antagonists marked the beginning of a new era in the management of PCa. 12 While LHRH agonists cause an initial testosterone surge that may result in a clinical flare of symptoms, 13 GnRH antagonists have been shown to offer rapid reduction of serum testosterone without the initial testosterone surge and symptoms flare. 1 The Phase III HERO study revealed rapid testosterone suppression to castration levels with the first oral GnRH antagonist, relugolix, which were then maintained throughout the treatment period.…”

Section: Kurt Millermentioning

confidence: 99%

Androgen Deprivation Therapy in Current Clinical Practice: Challenges and Future Perspective

Danks

2023

EMJ Urol

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Androgen deprivation therapy (ADT) has been used for many years for treating advanced prostate cancer (PCa) and remains the backbone of treatment. Luteinising hormone-releasing hormone (LHRH) receptor agonists are the most widely used ADT drugs. However, newer options, including gonadotropin releasing hormone (GnRH) receptor antagonists such as degarelix and relugolix, may be clinically more beneficial for some patients. GnRH antagonists reduce serum testosterone levels more rapidly than LHRH agonists, without an initial testosterone surge or subsequent microsurges. This article summarises a symposium delivered on 11th March 2023 at the 38th European Association of Urology (EAU) Annual Congress in Milan, Italy, where speakers from three different disciplines described challenges and future perspectives for ADT in current clinical practice. Kurt Miller, Urologist, Charité University Hospital, Berlin, Germany, described the evolution of ADT in the treatment of PCa, from early reports of the benefits of surgical castration to the recent development of oral treatment for chemical castration. Miller explained the acceleration in progress in ADT research over recent years, with the development of novel drugs, drug sequences, and combinations, which have transformed outcomes in PCa. Alberto Bossi, Radiation Oncologist, Amethyst Group, Institut Gustav Roussy (IGR), Paris, France, next described current challenges with ADT management, including outstanding questions about the personalisation of ADT. Finally, Patrick Davey, Consultant Cardiologist, Northampton General Hospital, UK, spoke about ways to maintain a healthy heart on hormone treatment, and noted that cardiovascular safety is a major challenge in the use of ADT. The meeting was chaired by Heather Payne, Consultant Clinical Oncologist, University College Hospital, London, UK, who introduced the speakers and co-ordinated a question-and-answer session at the end of the symposium.

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Section: Kurt Millermentioning

confidence: 99%

Androgen Deprivation Therapy in Current Clinical Practice: Challenges and Future Perspective

Danks

2023

EMJ Urol

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“…These receptors associated with their ligands promoted migration, proliferation, neuroendocrine differentiation, mitogenic signaling and invasion of PC [ 61 ]. Some small molecules have been tested to block these GPCRs as antagonists of gonadotropin-releasing hormone receptor (GnRH), named degarelix or endothelin A receptor antagonist under clinical trial [ 54 , 62 ]. Inversely, few GPCRs and their ligands were able to inhibit growth of prostate cancer cells.…”

Section: Orexins and Other Cancersmentioning

confidence: 99%

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

et al. 2021

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Over 20 years ago, orexin neuropeptides (Orexin-A/hypocretin-1 and Orexin-B/hypocretins-2) produced from the same precursor in hypothalamus were identified. These two neurotransmitters and their receptors (OX1R and OX1R), present in the central and peripheral nervous system, play a major role in wakefulness but also in drug addiction, food consumption, homeostasis, hormone secretion, reproductive function, lipolysis and blood pressure regulation. With respect to these biological functions, orexins were involved in various pathologies encompassing narcolepsy, neurodegenerative diseases, chronic inflammations, metabolic syndrome and cancers. The expression of OX1R in various cancers including colon, pancreas and prostate cancers associated with its ability to induce a proapoptotic activity in tumor cells, suggested that the orexins/OX1R system could have a promising therapeutic role. The present review summarizes the relationship between cancers and orexins/OX1R system as an emerging target.

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“…Figure 1 represents some thienopyrimidinecontaining drugs with varying profiles of biological activity. Relugolix (TAK-385), is a thienopyrimidine derivative that has completed phase III clinical trials and is being studied for its capacity to treat endometriosis and prostate carcinoma by acting as a gonadotropin-releasing hormone receptor (GnRHR) antagonist [24,25]. DDP-225 is another thienopyrimidine drug that entered phase II clinical trials and was designed to cure irritable bowel syndrome (IBS) and gastrointestinal tract (GIT) diseases by acting as a serotonin receptor (5-HT 3 ) antagonist and noradrenaline reuptake inhibitor [26,27].…”

Section: Introductionmentioning

confidence: 99%

Recent updates on thienopyrimidine derivatives as anticancer agents

et al. 2023

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Thienopyrimidine derivatives hold a unique place between fused pyrimidine compounds. They are important and widely represented in medicinal chemistry as they are structural analogs of purines. Thienopyrimidine derivatives have various biological activities. The current review discusses different synthetic methods for the preparation of heterocyclic thienopyrimidine derivatives. It also highlights the most recent research on the anticancer effects of thienopyrimidines through the inhibition of various enzymes and pathways, which was published within the last 9 years. Graphical Abstract

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Progress in Clinical Research on Gonadotropin-Releasing Hormone Receptor Antagonists for the Treatment of Prostate Cancer

Cited by 11 publications

References 61 publications

Androgen Deprivation Therapy in Current Clinical Practice: Challenges and Future Perspective

Androgen Deprivation Therapy in Current Clinical Practice: Challenges and Future Perspective

Orexins/Hypocretins and Cancer: A Neuropeptide as Emerging Target

Recent updates on thienopyrimidine derivatives as anticancer agents

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