Authors: R. Eaveri; A. Ben-Yehudah; H. Lorberboum-Galski

Source: Current Cancer Drug Targets, Volume 4, Number 8, December 2004 , pp. 673-687(15)

Publisher: Bentham Science Publishers

Abstract:

Colon, breast and lung adenocarcinomas - three of the major malignancies occurring in humans, together with ovarian, endometrial, kidney and liver adenocarcinomas, account for more then 50% of cancerrelated death. As the number of cancer-related deaths has not decreased in recent years, major efforts are being made to find new and more specific drugs for cancer treatment.

One of the approaches developed in recent years for targeted cancer therapy is the construction and use of chimeric proteins. Chimeric cytotoxins are a class of targeted molecules designed to recognize and specifically destroy cells over-expressing specific receptors. These molecules, designed and constructed by gene fusion techniques, comprise both the cell-targeting and the cell-killing moieties. Our laboratory has developed a number of chimeric proteins based on an analog of Gonadotropin Releasing Hormone (GnRH) as their targeting moiety. These chimeras recognize a GnRH-binding site that, we found, was over-expressed on a surprisingly wide variety of cancers, all confined to the adenocarcinoma type. A GnRH analog was fused to a large number of killing moieties, including bacterial or human pro-apoptotic proteins. All GnRH-based chimeric proteins selectively killed adenocarcinoma cells both in vitro and in vivo. Utilizing GnRH-based chimeric proteins for targeted therapy could open up new vistas in the fight against adenocarcinomas in humans.

This review summarizes the latest developments in the area of targeted cancer therapy via specific antigens/receptors, as well as our latest findings in targeting GnRH-binding sites using GnRH-based chimeric proteins for specific and targeted adenocarcinoma therapy in humans.

Keywords: targeted therapy; cancer; chimeric proteins; adenocarcinoma; gnrh-binding site; apoptosis

Document Type: Review article

DOI: http://dx.doi.org/10.2174/1568009043332745

Affiliations: 1: Department of Cellular Biochemistry and Human Genetics, Hebrew University-Hadassah Medical School, Jerusalem, 91120, Israel.

Publication date: 2004-12-01

More about this publication?

• Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes, genes.
  Each issue of the journal contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics on drug targets involved in cancer.
  As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.

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