Current Cancer Drug Targets

Ruiwen Zhang 
Texas Tech University Health Sciences Center
1300 Coulter Drive
Amarillo, TX 79106
USA

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Integrins in Cancer Treatment

Author(s): Johannes A. Eble, Jorg Haier.

Abstract:

Anchorage-independent growth, anoikis resistance, and most steps of metastasis formation are integrin-mediated or -dependent processes, which are characteristics of malignant tumor cells. Acting as oncogenes or tumor suppressor genes, integrins may be involved in the oncogenic transformation of normal cells and their growth into a primary tumor node. During tumorigenesis, a switch of integrin expression can be observed, inasmuch as growth-promoting and growth-attenuating integrins are up- and down-regulated, respectively. ECM-ligand binding to an integrin initiates signals, which eradiating from the integrins are transmitted via different yet interconnecting pathways and elicit various cell functions, such as morphological changes, adhesion, migration and gene activation. Any of these functions takes part in the metastatic cascade of tumor progression, such as epithelial-to-mesenchymal transition of carcinoma cells, tumor cell contact with the basement membrane, invasion into neighboring tissues as well as production and activation of ECM-degrading MMPs. Besides their direct involvement in tumor progression as cell surface molecules on tumor cells, integrins in normal cells surrounding a tumor, e.g. endothelial cells, can also determine various cancer characteristics, such as tumor-induced neoangiogenesis and immune resistance. Hence, integrins are relevant pharmacological targets in tumor biology. Spurred by the recent success to generate pharmaceutical mimetics of RGD-dependent integrins and by the integrins easy accessibility on the cell surface, the hope is rising that also RGD-independent integrins, such as the collagen- and laminin-binding integrins, can be pharmacologically manipulated to fight integrin-dependent functions of cancer cells, which are necessary and at least partially specific for their proliferation and progression

Keywords: Integrin, extracellular matrix, tumorigenesis, metastasis, tumor progression, tumor-induced angiogenesis

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Article Details

VOLUME: 6
ISSUE: 2
Year: 2006
Page: [89 - 105]
Pages: 17
DOI: 10.2174/156800906776056518
Price: $58