Conventional and new proposals of GnRH therapy for ovarian, breast, and prostatic cancers

Garrido, Maritza P.; Hernández, Andrea; Vega, Margarita; Araya, Eyleen; Romero, Carmen

doi:10.3389/fendo.2023.1143261

Cited by 5 publications

(6 citation statements)

References 111 publications

(130 reference statements)

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“…For decades, we have known that GnRH1 and GnRHR1 are expressed in reproductive tumors and GnRH1 analogues inhibit cancer cell proliferation (19,(33)(34)(35)(36)(37)(38). In fact, the newest approaches utilize GnRH1-tagged nanoparticles to directly target chemotherapeutics into cancer cells (39). In addition, elevated expression of GnRH1 and GnRHR1 in bladder cancer is linked with better survival in men but worse survival in women, suggesting possible regulation of the GnRH1/GnRHR1 system by gonadal steroids in non-reproductive tissues (40).…”

Section: Gnrh2 and Gnrhr2 In Human Reproductive Cancersmentioning

confidence: 99%

Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers

Desaulniers,

White

2024

Front. Endocrinol.

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Gonadotropin-releasing hormone (GnRH1) and its receptor (GnRHR1) drive reproduction by regulating gonadotropins. Another form, GnRH2, and its receptor (GnRHR2), also exist in mammals. In humans, GnRH2 and GnRHR2 genes are present, but coding errors in the GnRHR2 gene are predicted to hinder full-length protein production. Nonetheless, mounting evidence supports the presence of a functional GnRHR2 in humans. GnRH2 and its receptor have been identified throughout the body, including peripheral reproductive tissues like the ovary, uterus, breast, and prostate. In addition, GnRH2 and its receptor have been detected in a wide number of reproductive cancer cells in humans. Notably, GnRH2 analogues have potent anti-proliferative, pro-apoptotic, and/or anti-metastatic effects on various reproductive cancers, including endometrial, breast, placental, ovarian, and prostate. Thus, GnRH2 is an emerging target to treat human reproductive cancers.

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Section: Gnrh2 and Gnrhr2 In Human Reproductive Cancersmentioning

confidence: 99%

Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers

Desaulniers,

White

2024

Front. Endocrinol.

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“… Name Company Year Targets Used for Refs. Leuprorelin, Lupron, Viadur, Eligard, Fensolvi Abbott Laboratories, Abbott Park, IL, USA 1985 GnRH receptor Prostate cancer, breast cancer [ 173 , 174 ] Goserelin, Zoladex TerSera therapeutics, Deerfield, IL, USA 1997 GnRH receptor Prostate cancer, breast cancer, endometriosis [ 175 , 176 ] Octreotide, Sandostatin Novartis, Basel, Switzerland 1998 Reduction of growth hormone treat diarrhea or diarrhea associated with some types of cancer [ 177 ] Cetrorelix, Cetrotide Merck Serono, Darmstadt, Germany 2000 GnRH receptor In vitro fertilization [ 175 ] Abarelix, Plenaxis Praecis Pharmaceuticals, Waltham, MA, USA 2003 GnRH receptor Advanced prostate cancer [ 9 ] Degarelix, Firmagon …”

Section: Peptide-based Approaches For Cancer Treatmentmentioning

confidence: 99%

“…For instance, Leuprorelin (Abbott Laboratories, Abbott Park, IL, USA), Goserelin (TerSera therapeutics, Deerfield, IL, USA), and Cetrorelix (Merck Serono, Darmstadt, Germany) have been used for breast cancer and prostate cancer patients. They are designed as hormone analogs and rapidly absorbed following subcutaneous injection [ 173 , 174 , 175 , 176 ]. Although the traditional route of administering protein and peptide-based drugs using a needle and syringe is commonly practiced, it has certain limitations, such as patient comfort, cost, sterility, etc.…”

Section: Peptides In Applicationsmentioning

confidence: 99%

“…2023, 24, x FOR PEER REVIEW 11 of 37 prostate cancer patients. They are designed as hormone analogs and rapidly absorbed following subcutaneous injection [173][174][175][176]. Although the traditional route of administering protein and peptide-based drugs using a needle and syringe is commonly practiced, it has certain limitations, such as patient comfort, cost, sterility, etc.…”

Section: Oral Routementioning

confidence: 99%

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Peptide-Based Agents for Cancer Treatment: Current Applications and Future Directions

Nhàn,

Yamada,

Yamada

2023

IJMS

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Peptide-based strategies have received an enormous amount of attention because of their specificity and applicability. Their specificity and tumor-targeting ability are applied to diagnosis and treatment for cancer patients. In this review, we will summarize recent advancements and future perspectives on peptide-based strategies for cancer treatment. The literature search was conducted to identify relevant articles for peptide-based strategies for cancer treatment. It was performed using PubMed for articles in English until June 2023. Information on clinical trials was also obtained from ClinicalTrial.gov. Given that peptide-based strategies have several advantages such as targeted delivery to the diseased area, personalized designs, relatively small sizes, and simple production process, bioactive peptides having anti-cancer activities (anti-cancer peptides or ACPs) have been tested in pre-clinical settings and clinical trials. The capability of peptides for tumor targeting is essentially useful for peptide–drug conjugates (PDCs), diagnosis, and image-guided surgery. Immunomodulation with peptide vaccines has been extensively tested in clinical trials. Despite such advantages, FDA-approved peptide agents for solid cancer are still limited. This review will provide a detailed overview of current approaches, design strategies, routes of administration, and new technological advancements. We will highlight the success and limitations of peptide-based therapies for cancer treatment.

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“…Clearly, melatonin-GR interactions will influence hypothalamic fluxes that may be differentially relevant in different types of cancer, such as gonadotrophin releasing hormone (GnRH) regulation of pituitary luteinizing hormone in the regulation of ovarian, breast and prostate cancers [ 139 – 141 ], with relevance as to how other types of ovarian conditions, such as polycystic ovary syndrome (PCOS) [ 142 , 143 ] and endometriosis [ 144 , 145 ], are associated with ovarian and breast cancer risk. Such data highlights the magnitude of factors that can influence intercellular interactions in the tumor microenvironment, whilst also indicating the importance of melatonin/BAG-1/CAR-GR interactions over the circadian rhythm in coordinating hypothalamic function with wider physiological processes across different organs and tissues.…”

Section: Hypothalamic Interactions Of Melatonin Gr and Trkb In Tumor ...mentioning

confidence: 99%

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

Anderson

2023

Exploration of Targeted Anti-Tumor Therapy

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A dysregulated circadian rhythm is significantly associated with cancer risk, as is aging. Both aging and circadian dysregulation show suppressed pineal melatonin, which is indicated in many studies to be linked to cancer risk and progression. Another independently investigated aspect of the circadian rhythm is the cortisol awakening response (CAR), which is linked to stress-associated hypothalamus-pituitary-adrenal (HPA) axis activation. CAR and HPA axis activity are primarily mediated via activation of the glucocorticoid receptor (GR), which drives patterned gene expression via binding to the promotors of glucocorticoid response element (GRE)-expressing genes. Recent data shows that the GR can be prevented from nuclear translocation by the B cell lymphoma-2 (Bcl-2)-associated athanogene 1 (BAG-1), which translocates the GR to mitochondria, where it can have diverse effects. Melatonin also suppresses GR nuclear translocation by maintaining the GR in a complex with heat shock protein 90 (Hsp90). Melatonin, directly and/or epigenetically, can upregulate BAG-1, suggesting that the dramatic 10-fold decrease in pineal melatonin from adolescence to the ninth decade of life will attenuate the capacity of night-time melatonin to modulate the effects of the early morning CAR. The interactions of pineal melatonin/BAG-1/Hsp90 with the CAR are proposed to underpin how aging and circadian dysregulation are associated with cancer risk. This may be mediated via differential effects of melatonin/BAG-1/Hsp90/GR in different cells of microenvironments across the body, from which tumors emerge. This provides a model of cancer pathogenesis that better integrates previously disparate bodies of data, including how immune cells are regulated by cancer cells in the tumor microenvironment, at least partly via the cancer cell regulation of the tryptophan-melatonin pathway. This has a number of future research and treatment implications.

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Conventional and new proposals of GnRH therapy for ovarian, breast, and prostatic cancers

Cited by 5 publications

References 111 publications

Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers

Role of gonadotropin-releasing hormone 2 and its receptor in human reproductive cancers

Peptide-Based Agents for Cancer Treatment: Current Applications and Future Directions

Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses

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