Authors: Goh, P. P.; Sze, D. M.; Roufogalis, B. D.

Source: Current Cancer Drug Targets, Volume 7, Number 8, December 2007 , pp. 743-758(16)

Publisher: Bentham Science Publishers

Abstract:

Current cancer chemotherapeutic drugs have limited efficacy due to the fact that tumour cells are a rapidly changing target characterised by genomic instability. Unlike tumour cells, activated endothelial cells (ECs) required for angiogenesis, a process indisputably crucial to tumour growth and metastasis, were originally considered to be ideal therapeutic targets free of drug resistance. Additionally, unlike preclinical studies in mice using inhibitors targeting the powerful EC mitogen- vascular endothelial growth factor (VEGF)- overall survival benefit with anti-VEGF therapy used as monotherapy has yet to be demonstrated in phase III clinical trials. In contrast, VEGF-specific antibodies combined with current chemotherapy have resulted in improved outcomes in certain previously untreated cancers. This has led some researchers to hypothesize that combined treatments targeting other angiogenic molecules besides VEGF, and/or targeting not only ECs but other angiogenic non-EC types, may offer alternative but effective therapeutic options for eradicating malignant tumours. A rational approach to effective anti-angiogenic combination therapy will, however, require further understanding of the molecular and cellular mechanisms which undergird tumour vascularisation. Recent studies involving judicious use of powerful new genetic approaches have provided unprecedented insights into how different molecular and cellular mechanisms cooperate to build, branch and mature the growing vessel network so pivotal to tumour growth and survival. This review covers our current understanding of how the various key players - the tumour cells, stromal cells, endothelial cells and pericytes, and bone-marrowderived haematopoietic and putative endothelial progenitors interact via their cell-derived pro- or anti-angiogenic factors to regulate tumour angiogenesis.

Keywords: Tumour angiogenesis; haematopoietic cells; endothelial progenitor cells; angiogenic factors; adhesion molecules; proteolytic enzymes

Document Type: Research article

DOI: http://dx.doi.org/10.2174/156800907783220462

Publication date: 2007-12-01

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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