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Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects

Tumour invasion and metastasis have been recognized as major causal factors in the morbidity and mortality among cancer patients. Many advances in the knowledge of cancer metastasis have yielded an impressive array of attractive drug targets, including enzymes, receptors and multiple signalling path...

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Main Authors: Wong, Mei S., Mohd Sidik, Shiran, Mahmud, Rozi, Stanslas, Johnson
Format: Article
Language:English
Published: Wiley-Blackwell Publishing Asia 2013
Online Access:http://psasir.upm.edu.my/id/eprint/29722/1/Molecular%20targets%20in%20the%20discovery%20and%20development%20of%20novel%20antimetastatic%20agents.pdf
http://psasir.upm.edu.my/id/eprint/29722/
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spelling my.upm.eprints.297222015-10-09T01:01:10Z http://psasir.upm.edu.my/id/eprint/29722/ Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects Wong, Mei S. Mohd Sidik, Shiran Mahmud, Rozi Stanslas, Johnson Tumour invasion and metastasis have been recognized as major causal factors in the morbidity and mortality among cancer patients. Many advances in the knowledge of cancer metastasis have yielded an impressive array of attractive drug targets, including enzymes, receptors and multiple signalling pathways. The present review summarizes the molecular pathogenesis of metastasis and the identification of novel molecular targets used in the discovery of antimetastatic agents. Several promising targets have been highlighted, including receptor tyrosine kinases, effector molecules involved in angiogenesis, matrix metalloproteinases (MMPs), urokinase plasminogen activator, adhesion molecules and their receptors, signalling pathways (e.g. phosphatidylinositol 3-kinase, phospholipase Cγ1, mitogen-activated protein kinases, c-Src kinase, c-Met kinases and heat shock protein. The discovery and development of potential novel therapeutics for each of the targets are also discussed in this review. Among these, the most promising agents that have shown remarkable clinical outcome are anti-angiogenic agents (e.g. bevacizumab). Newer agents, such as c-Met kinase inhibitors, are still undergoing preclinical studies and are yet to have their clinical efficacy proven. Some therapeutics, such as first-generation MMP inhibitors (MMPIs; e.g. marimastat) and more selective versions of them (e.g. prinomastat, tanomastat), have undergone clinical trials. Unfortunately, these drugs produced serious adverse effects that led to the premature termination of their development. In the future, third-generation MMPIs and inhibitors of signalling pathways and adhesion molecules could form valuable novel classes of drugs in the anticancer armamentarium to combat metastasis. Wiley-Blackwell Publishing Asia 2013-05 Article PeerReviewed application/pdf en http://psasir.upm.edu.my/id/eprint/29722/1/Molecular%20targets%20in%20the%20discovery%20and%20development%20of%20novel%20antimetastatic%20agents.pdf Wong, Mei S. and Mohd Sidik, Shiran and Mahmud, Rozi and Stanslas, Johnson (2013) Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects. Clinical and Experimental Pharmacology and Physiology, 40 (5). pp. 307-319. ISSN 0305-1870; ESSN: 1440-1681 10.1111/1440-1681.12083
institution Universiti Putra Malaysia
building UPM Library
collection Institutional Repository
continent Asia
country Malaysia
content_provider Universiti Putra Malaysia
content_source UPM Institutional Repository
url_provider http://psasir.upm.edu.my/
language English
description Tumour invasion and metastasis have been recognized as major causal factors in the morbidity and mortality among cancer patients. Many advances in the knowledge of cancer metastasis have yielded an impressive array of attractive drug targets, including enzymes, receptors and multiple signalling pathways. The present review summarizes the molecular pathogenesis of metastasis and the identification of novel molecular targets used in the discovery of antimetastatic agents. Several promising targets have been highlighted, including receptor tyrosine kinases, effector molecules involved in angiogenesis, matrix metalloproteinases (MMPs), urokinase plasminogen activator, adhesion molecules and their receptors, signalling pathways (e.g. phosphatidylinositol 3-kinase, phospholipase Cγ1, mitogen-activated protein kinases, c-Src kinase, c-Met kinases and heat shock protein. The discovery and development of potential novel therapeutics for each of the targets are also discussed in this review. Among these, the most promising agents that have shown remarkable clinical outcome are anti-angiogenic agents (e.g. bevacizumab). Newer agents, such as c-Met kinase inhibitors, are still undergoing preclinical studies and are yet to have their clinical efficacy proven. Some therapeutics, such as first-generation MMP inhibitors (MMPIs; e.g. marimastat) and more selective versions of them (e.g. prinomastat, tanomastat), have undergone clinical trials. Unfortunately, these drugs produced serious adverse effects that led to the premature termination of their development. In the future, third-generation MMPIs and inhibitors of signalling pathways and adhesion molecules could form valuable novel classes of drugs in the anticancer armamentarium to combat metastasis.
format Article
author Wong, Mei S.
Mohd Sidik, Shiran
Mahmud, Rozi
Stanslas, Johnson
spellingShingle Wong, Mei S.
Mohd Sidik, Shiran
Mahmud, Rozi
Stanslas, Johnson
Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
author_facet Wong, Mei S.
Mohd Sidik, Shiran
Mahmud, Rozi
Stanslas, Johnson
author_sort Wong, Mei S.
title Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
title_short Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
title_full Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
title_fullStr Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
title_full_unstemmed Molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
title_sort molecular targets in the discovery and development of novel antimetastatic agents: current progress and future prospects
publisher Wiley-Blackwell Publishing Asia
publishDate 2013
url http://psasir.upm.edu.my/id/eprint/29722/1/Molecular%20targets%20in%20the%20discovery%20and%20development%20of%20novel%20antimetastatic%20agents.pdf
http://psasir.upm.edu.my/id/eprint/29722/
_version_ 1643829845414641664
score 13.211869

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