title: Targeting luteinizing hormone-releasing hormone: A potential therapeutics to treat gynecological and other cancers.
abstract: Cancer is a prime healthcare problem that is significantly responsible for universal mortality. Despite distinguished advancements in medical field, chemotherapy is still the mainstay for the treatment of cancers. During chemotherapy, approximately 90% of the administered dose goes to normal tissues, with mere 2-5% precisely reaching the cancerous tissues. Subsequently, the resultant side effects and associated complications lead to dose reduction or even discontinuance of the therapy. Tumor directed therapy therefore, represents a fascinating approach to augment the therapeutic potential of anticancer bioactives as well as overcomes its side effects. The selective overexpression of LHRH receptors on human tumors compared to normal tissues makes them a suitable marker for diagnostics, molecular probes and targeted therapeutics. These understanding enabled the rational to conjugate LHRH with various cytotoxic drugs (doxorubicin, DOX; camptothecin etc.), cytotoxic genes [small interfering RNA (siRNA), micro RNA (miRNA)], as well as therapeutic nanocarriers (nanoparticles, liposomes or dendrimers) to facilitate their tumor specific delivery. LHRH conjugation enhances their delivery via LHRH receptor mediated endocytosis. Numerous cytotoxic analogs of LHRH were developed over the past two decades to target various types of cancers. The potency of LHRH compound were reported to be as high as 5,00-10,00 folds compared to parent molecules. The objective of this review article is to discuss reports on various LHRH analogs with special emphasis on their prospective application in the medical field. The article also focuses on the attributes that must be taken into account while designing a LHRH therapeutics with special account to the biochemistry and applications of these conjugates. The record on various cytotoxic analogs of LHRH are also discussed. It is anticipated that the knowledge of therapeutic and toxicological aspects of LHRH compounds will facilitate the development of a more systematic approach to the targeted delivery of cytotoxic agents using peptides.
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, MP 470 003, India.
authors.forename: Raksha
authors.initials: R
authors.lastname: Ghanghoria
authors.affiliation: Pharmaceutics Division, CSIR-Central Drug Research Institute, Lucknow, UP, 226031 India. Electronic address: prashantdops@gmail.com.
authors.forename: Prashant
authors.initials: P
authors.lastname: Kesharwani
authors.affiliation: The International Medical University, School of Pharmacy, Department of Pharmaceutical Technology, JalanJalil Perkasa 19, 57000 Kuala Lumpur, Malaysia; National Institute of Pharmaceutical Education and Research (NIPER) - Ahmedabad, Opposite Air Force Station Palaj, Gandhinagar, Gujarat 382355, India.
authors.forename: Rakesh K
authors.initials: RK
authors.lastname: Tekade
authors.affiliation: Pharmaceutics Research Laboratory, Department of Pharmaceutical Sciences, Dr. Hari Singh Gour University, Sagar, MP 470 003, India. Electronic address: jnarendr@yahoo.co.in.
authors.forename: Narendra K
authors.initials: NK
authors.lastname: Jain
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D007987:Gonadotropin-Releasing Hormone / Q000008:administration & dosage* / Q000031:analogs & derivatives; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D011966:Receptors, LHRH / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone
keywords: Binding mechanics; Cancer targeting; Clinical trials; LHRH analogs; Toxicological issues