摘要
促黄体激素释放激素(luteinizing hormone-releasing hormone)受体的表达80%左右在人子宫内膜癌、卵巢癌和前列腺癌中也发现在50%以上的乳腺癌癌症包括三阴性乳腺癌中。在人体中,促黄体激素释放激素受体被发现在垂体及生殖器官有显著水平。其他良性组织或造血干细胞只表达低水平的促黄体激素释放激素受体或无受体。因此,促黄体激素释放激素受体有前景作为以细胞毒性混合分子介导的化学疗法的靶点受体。促黄体激素释放激素细胞毒类似物包括促黄体激素释放激素受体激动剂,它被用来作为一个载体肽和阿霉素或其衍生物。促黄体激素释放激素类似物的细胞毒性,AEZS-108(原名为AN-152)和AN-207,在多种促黄体激素释放激素受体体外和在体内阳性肿瘤模型中具有抗癌活性。在AEZS-108(原名DOX)阿霉素共价连接到促黄体激素释放激素激动剂[D-Lys6] 促黄体激素释放激素。第一和第二阶段的在乳腺癌、子宫内膜癌和卵巢癌患者临床研究中表现出良好的抗癌活性,可调和的毒副作用以及到目前为止无任何毒性。AEZS-108也在第一第二期阉割研究中被评价为能抵抗前列腺癌和转移性膀胱癌。因为第二阶段在子宫内膜癌的结果前景大,所以多国、多中心第三阶段研究恶性肿瘤已启动,目前正在招募的病人。
关键词: 促黄体激素释放激素受体
图形摘要
Current Drug Targets
Title:Targeting of Peptide Cytotoxins to LHRH Receptors For Treatment of Cancer
Volume: 17 Issue: 5
Author(s): Jörg B. Engel, Hans-Rudolf Tinneberg, Ferenc G. Rick, Enniko Berkes and Andrew V. Schally
Affiliation:
关键词: 促黄体激素释放激素受体
摘要: Receptors for LHRH (luteinizing hormone-releasing hormone) are expressed in about 80% of human endometrial, ovarian and prostate cancers and are also found in more than 50% of breast cancers including triple negative breast cancers. In the human body, LHRH receptors are found at significant levels in the pituitary and reproductive organs. Other benign tissues or hematopoietic stem cells express only low levels of receptors for LHRH or no receptors. Thus LHRH receptors are promising targets for a receptor- mediated chemotherapy with cytotoxic hybrid molecules. Cytotoxic analogs of LHRH consist of a LHRH agonist, which is used as a carrier peptide and DOX or its derivatives. Cytotoxic analogs of LHRH, AEZS-108 (formerly known as AN-152) and AN-207, exhibit anti-cancer activity in various in vitro and in vivo models of LHRH-receptor positive cancers. In AEZS-108 (zoptarelin DOX) DOX is covalently linked to the LHRH agonist [D-Lys6]LHRH. Results of phase I and II clinical studies in patients with breast, endometrial and ovarian cancers demonstrated good anticancer activity with moderate toxic side effects and without any sign of cardiotoxicity so far. AEZS-108 is also being evaluated in phase I/II studies in castration resistant prostate cancer and metastatic bladder cancer. Because of the very promising phase II results in endometrial cancer, a multinational, multicenter phase III study of this malignancy has been initiated and is currently recruiting patients.
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Jörg B. Engel, Hans-Rudolf Tinneberg, Ferenc G. Rick, Enniko Berkes and Andrew V. Schally , Targeting of Peptide Cytotoxins to LHRH Receptors For Treatment of Cancer, Current Drug Targets 2016; 17 (5) . https://dx.doi.org/10.2174/138945011705160303154717
DOI https://dx.doi.org/10.2174/138945011705160303154717 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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