Targeted chemotherapy of endometrial, ovarian and breast cancers with cytotoxic analogs of luteinizing hormone-releasing hormone (LHRH)

Archives of Gynecology and Obstetrics
J B EngelO Ortmann

Abstract

Receptors luteinizing hormone-releasing hormone (LHRH) are expressed in about 80 % of human endometrial and ovarian cancers and account for more than 50 % of breast cancers including triple negative breast cancers. Apart from the pituitary and reproductive organs, no other organs or hematopoietic stem cells express LHRH (GnRH) receptors. Thus, these receptors can be regarded as an ideal target for a personalized medicine approach in cancer therapy. AEZS-108 (formerly known as AN-152) in which doxorubin is linked to the LHRH agonist [D: -Lys(6)]LHRH, appears to be the most advanced compound in late stage clinical development. Results of phase I and phase II clinical trials in patients with gynecological cancers demonstrated anticancer activity without any cardiotoxicity even in highly pretreated patients. AEZS-108 is therefore being considered for phase II trials in triple negative breast cancers and phase III studies in advanced endometrial cancers positive for LHRH-receptor. EP-100 is a membrane-disrupting peptide targeted to LHRH receptors, which is undergoing early clinical studies in ovarian cancer patients.

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Citations

Apr 29, 2014·Taiwanese Journal of Obstetrics & Gynecology·Kuan-Hao TsuiChih-Ping Chen
Dec 31, 2015·Human Reproduction Update·Roberto MaggiPatrizia Limonta
Mar 12, 2016·Hormone Molecular Biology and Clinical Investigation·Areege KamalDharani K Hapangama
Apr 15, 2016·Archives of Gynecology and Obstetrics·Wenjuan LiShanyu Fang
Nov 5, 2003·Reproductive Biology and Endocrinology : RB&E·Carsten Gründker, Günter Emons
Sep 25, 2014·The Journal of Antibiotics·Chathurada GajadeeraOleg V Tsodikov
Oct 6, 2017·Oncotarget·Sander R DubovyAndrew V Schally
Sep 18, 2016·Hormone Molecular Biology and Clinical Investigation·Chenthuran DeivarajuAndrew V Schally
Jul 17, 2019·Current Medicinal Chemistry·Haralambos TzoupisTheodore Tselios
Jul 26, 2021·European Journal of Medicinal Chemistry·Jiaqi ZhouHai Qian

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