Issue 27, 2012

Targeted therapy vs. DNA-adduct formation-guided design: thoughts about the future of metal-based anticancer drugs

Abstract

The development of metal-based anticancer drugs is mainly governed by the experience accumulated with cisplatin and its analogues. The synthesis is focused on adding appropriate leaving and non-leaving groups to a transition metal in order to get more favorable DNA binding properties, and the biological activity is tested in vitro, always in a second step, looking for the cell line that is killed at the lowest drug concentration. This strategy seems unproductive today for the area of new drug development where the knowledge on cancer genomics is suggesting the use of targets selectively expressed, or overexpressed by cancer cells. These targets almost always are proteins, constituting membrane receptors or components of crucial biochemical pathways. Some data indicate that the antitumor activity of cisplatin might also be due to the interaction with protein targets. This critical review examines the possibilities for metal-based drugs to challenge tumors with innovative strategies, based on genomic approaches, capitalizing on the chemical experiences with metals in medicine and focusing on the nature of the ligands which are added to a metal depending on the selected tumor cells and on their molecular targets.

Graphical abstract: Targeted therapy vs. DNA-adduct formation-guided design: thoughts about the future of metal-based anticancer drugs

Article information

Article type
Perspective
Submitted
11 Jan 2012
Accepted
25 Apr 2012
First published
01 May 2012

Dalton Trans., 2012,41, 8226-8234

Targeted therapy vs. DNA-adduct formation-guided design: thoughts about the future of metal-based anticancer drugs

G. Sava, G. Jaouen, E. A. Hillard and A. Bergamo, Dalton Trans., 2012, 41, 8226 DOI: 10.1039/C2DT30075C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements