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Validating matrix metalloproteinases as drug targets and anti-targets for cancer therapy
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The matrix metalloproteinases mediate homeostasis of the extracellular environment and have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs.Abstract:
The matrix metalloproteinases (MMPs) mediate homeostasis of the extracellular environment. They have multiple signalling activities that are commonly altered during tumorigenesis and that might serve as intervention points for anticancer drugs. However, there are many criteria to consider in validating MMPs as drug targets and for the development of MMP inhibitors. The inhibition of some MMPs could have pro-tumorigenic effects (making them anti-targets), counterbalancing the benefits of target inhibition. These effects might partially account for the failure of MMP inhibitors in clinical trials. What are the major challenges in MMP target validation and MMP-inhibitor-drug development?read more
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Chemokine: receptor structure, interactions, and antagonism.
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Matrix metalloproteinases as novel biomarkers and potential therapeutic targets in human cancer.
TL;DR: The matrix metalloproteinase (MMP) family of enzymes is comprised of critically important extracellular matrix remodeling proteases whose activity has been implicated in a number of key normal and pathologic processes.
References
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Journal ArticleDOI
Inflammation and cancer
Lisa M. Coussens,Zena Werb +1 more
TL;DR: It is now becoming clear that the tumour microenvironment, which is largely orchestrated by inflammatory cells, is an indispensable participant in the neoplastic process, fostering proliferation, survival and migration.
Journal ArticleDOI
Gene expression profiling predicts clinical outcome of breast cancer
Laura J. van't Veer,Hongyue Dai,Marc J. van de Vijver,Yudong D. He,Augustinus A. M. Hart,Mao Mao,Hans Peterse,Karin van der Kooy,Matthew J. Marton,Anke T. Witteveen,George J. Schreiber,Ron M. Kerkhoven,Christopher J. Roberts,Peter S. Linsley,René Bernards,Stephen H. Friend +15 more
TL;DR: DNA microarray analysis on primary breast tumours of 117 young patients is used and supervised classification is applied to identify a gene expression signature strongly predictive of a short interval to distant metastases (‘poor prognosis’ signature) in patients without tumour cells in local lymph nodes at diagnosis, providing a strategy to select patients who would benefit from adjuvant therapy.
Journal ArticleDOI
Patterns and Emerging Mechanisms of the Angiogenic Switch during Tumorigenesis
TL;DR: The work from the authors' laboratories reviewed herein was supported by grants from the National Cancer Institute.
Journal ArticleDOI
Mass spectrometry-based proteomics
Ruedi Aebersold,Matthias Mann +1 more
TL;DR: The ability of mass spectrometry to identify and, increasingly, to precisely quantify thousands of proteins from complex samples can be expected to impact broadly on biology and medicine.
Journal ArticleDOI
New functions for the matrix metalloproteinases in cancer progression
Mikala Egeblad,Zena Werb +1 more
TL;DR: It is shown that the MMPs have functions other than promotion of invasion, have substrates other than components of the extracellular matrix, and that they function before invasion in the development of cancer.
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