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

Arch Gynecol Obstet. 2012 Aug;286(2):437-42. doi: 10.1007/s00404-012-2335-1. Epub 2012 May 4.

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.

Publication types

  • Review

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use*
  • Breast Neoplasms / drug therapy*
  • Clinical Trials, Phase I as Topic
  • Clinical Trials, Phase II as Topic
  • Clinical Trials, Phase III as Topic
  • Dogs
  • Doxorubicin / analogs & derivatives*
  • Doxorubicin / therapeutic use
  • Endometrial Neoplasms / drug therapy*
  • Female
  • Gonadotropin-Releasing Hormone / analogs & derivatives*
  • Gonadotropin-Releasing Hormone / therapeutic use
  • Humans
  • Mice
  • Molecular Targeted Therapy / methods*
  • Ovarian Neoplasms / drug therapy*
  • Precision Medicine / methods
  • Rats

Substances

  • Antineoplastic Agents
  • LHRH, lysine(6)-doxorubicin
  • Gonadotropin-Releasing Hormone
  • Doxorubicin