Targeting to Peptide Receptors

Schally, Andrew V.; Halmos, Gábor

doi:10.1002/9783527634057.ch38

Cited by 9 publications

(54 citation statements)

References 119 publications

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“…The presence of LH-RH-R in various types of cancers and cancer cell lines originating from organs other than those of the reproductive system has been shown in various studies (14,16–19,21,30). Both agonists and antagonists of LH-RH may serve as potential therapeutic agents, acting directly on the target cancer cells (16,17,30–32). LH-RH agonists inhibit the gonadotropin secretion after continuous exposure (31).…”

Section: Discussionmentioning

confidence: 92%

“…We previously demonstrated that LH-RH-R is expressed in approximately half (47%) of human UMs (24). The effects of LH-RH and its analogs are mediated by high-affinity G-protein-coupled receptors for LH-RH located on the membranes of the pituitary gonadotrophs and different human types of cancers (16,17,19–21). The presence of LH-RH-R in various types of cancers and cancer cell lines originating from organs other than those of the reproductive system has been shown in various studies (14,16–19,21,30).…”

Section: Discussionmentioning

confidence: 99%

“…The effects of LH-RH and its analogs are mediated by high-affinity G-protein-coupled receptors for LH-RH located on the membranes of the pituitary gonadotrophs and different human types of cancers (16,17,19–21). The presence of LH-RH-R in various types of cancers and cancer cell lines originating from organs other than those of the reproductive system has been shown in various studies (14,16–19,21,30). Both agonists and antagonists of LH-RH may serve as potential therapeutic agents, acting directly on the target cancer cells (16,17,30–32).…”

Section: Discussionmentioning

confidence: 99%

“…In contrast, antagonists of LH-RH produce a competitive blockade of LH-RH-R leading to an immediate cessation of the secretion of gonadotropins and sex steroids, reducing the time of the onset of therapeutic effects compared to the agonists (33). Agonistic analogs, such as triptorelin, leuprolelin, goserelin and buserelin are extensively applied in gynecology and oncology (14,16–18,30). Potent antagonists of LH-RH, such as cetrorelix, ganirelix, abarelix and degarelix, have also been developed and are now available for clinical use (14,16–18,30,33).…”

Section: Discussionmentioning

confidence: 99%

“…Tumoral receptors for LH-RH have been detected on human breast, prostatic, ovarian, endometrial and pancreatic cancers and in human melanomas, non-Hodgkin's lymphomas and renal cell carcinomas (14–20). Over the past decade, a direct receptor-mediated antiproliferative effect of LH-RH-analogs on tumor cells was proposed (14,16,17,19–21). The receptors for LH-RH (LH-RH-R) on human tumors can also serve as targets for LH-RH analogs linked to various cytotoxic agents (15–17,22,23).…”

Section: Introductionmentioning

confidence: 99%

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Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

et al. 2017

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Uveal melanoma (UM) is the most common primary intraocular malignancy with a very poor prognosis. The most frequent chromosome aberration in UM is the monosomy of chromosome 3. Previously, we demonstrated that ~50% of UMs express type-I receptor for luteinizing hormone-releasing hormone (LH-RH-R). The gene encoding LH-RH-R is located in chromosome 4 (location: 4q21.2); however, the occurrence of numerical aberrations of chromosome 4 have never been studied in UM. In the present study, we investigated the abnormalities of chromosome 3 and 4, and the possible correlation between them, as well as with LH-RH-R expression. Forty-six specimens of UM were obtained after enucleation. Numerical aberrations of chromosome 3 and 4 were studied by fluorescence in situ hybridization (FISH). Chromosome 4 was detected in normal biparental disomy only in 14 (30%) samples; however, 32 cases (70%) showed more than 2 signals/nucleus. Monosomy of chromosome 3 could be found in 16 (35%) samples. In 6 specimens (13%), more than 2 copies of chromosome 3 were found, while normal biparental disomy was detected in 24 (52%) samples. Statistical analysis indicated a statistically significant (p<0.05) correlation between the copy number of chromosome 3 and 4. Moreover, moderate difference was revealed in the survival rate of the UM patients with various pathological profiles. No correlation was found between chromosome aberrations and LH-RH-R expression. Our results clearly demonstrate abnormalities in chromosome 3 and 4 and the incidence of the monosomy of chromosome 3 in human UM. In summary, our results provide new incite concerning the genetic background of this tumor. Our findings could contribute to a more precise determination of the prognosis of human UM and to the development of new therapeutic approaches to this malignancy.

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Section: Discussionmentioning

confidence: 92%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

et al. 2017

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Discovery of LHRH and development of LHRH analogs for prostate cancer treatment

2017

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The discovery, isolation, elucidation of structure, synthesis, and initial testing of the neuropeptide hypothalamic luteinizing hormone-releasing hormone (LHRH), which regulates reproduction, is briefly described. The design, synthesis, and experimental and clinical testing of agonistic analogs of LHRH is extensively reviewed focusing on the development of new methods for the treatment of prostate cancer. Subsequent development of antagonistic analogs of LHRH is then faithfully recounted with special emphasis on therapy of prostate cancer and BPH. The concepts of targeted therapy to peptide receptors on tumors are re-examined and the development of the cytotoxic analogs of LHRH and their status is reviewed. The endeavor to develop better therapies for prostate cancer, based on LHRH analogs, guided much of our work.

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Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

et al. 2013

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Uveal melanoma is the most common primary intraocular malignancy in adults, with a very high mortality rate due to frequent liver metastases. Consequently, the therapy of uveal melanoma remains a major clinical challenge and new treatment approaches are needed. For improving diagnosis and designing a rational and effective therapy, it is essential to elucidate molecular characteristics of this malignancy. The aim of this study therefore was to evaluate as a potential therapeutic target the expression of luteinizing hormone-releasing hormone (LHRH) receptor in human uveal melanoma. The expression of LHRH ligand and LHRH receptor transcript forms was studied in 39 human uveal melanoma specimens by RT-PCR using gene specific primers. The binding charachteristics of receptors for LHRH on 10 samples were determined by ligand competition assays. The presence of LHRH receptor protein was further evaluated by immunohistochemistry. The expression of mRNA for type I LHRH receptor was detected in 18 of 39 (46%) of tissue specimens. mRNA for LHRH-I ligand could be detected in 27 of 39 (69%) of the samples. Seven of 10 samples investigated showed high affinity LHRH-I receptors. The specific presence of full length LHRH receptor protein was further confirmed by immunohistochemistry. A high percentage of uveal melanomas express mRNA and protein for type-I LHRH receptors. Our results support the merit of further investigation of LHRH receptors in human ophthalmological tumors. Since diverse analogs of LHRH are in clinical trials or are already used for the treatment of various cancers, these analogs could be considered for the LHRH receptor-based treatment of uveal melanoma.

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Targeting to Peptide Receptors

Cited by 9 publications

References 119 publications

Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

Concurrence of chromosome 3 and 4 aberrations in human uveal melanoma

Discovery of LHRH and development of LHRH analogs for prostate cancer treatment

Substantial expression of luteinizing hormone-releasing hormone (LHRH) receptor type I in human uveal melanoma

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