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Small molecule alpha(v) integrin antagonists: novel anticancer agents
J S Kerr1, A M Slee, S A Mousa
1General Pharmacology, DuPont Pharmaceuticals Co., Route 141 and Henry Clay Road, PO Box 80400, Wilmington, DE 19880-0400, USA.
Abstract:
The members of the integrin family are targets that potentially provide both therapeutic and diagnostic opportunities. Advances in the understanding of the signalling pathways, transcriptional regulation and the structure/function relationships of the adhesion molecules to extracellular matrix proteins have all contributed to these opportunities. The role of the integrins in pathological processes in both acute and chronic diseases, include ocular, cancer (solid tumours and metastasis), cardiovascular (stroke and heart failure) and inflammatory (rheumatoid arthritis) conditions. Various therapeutic candidates, including antibodies, cyclic peptides and peptidomimetics, have been identified. This review will focus on the key role of the alpha(v) integrin (alpha(v)beta(3) and alpha(v)beta(5)) in angiogenic processes in tumours, including its potential use in cancer diagnostics and therapy.
Insights
Integrins are key targets for cancer diagnostics and therapy. This review highlights alpha(v) integrins, crucial for tumor angiogenesis, and their therapeutic potential.
Area of Science:
- Molecular Biology
- Oncology
- Pharmacology
Background:
- Integrins are cell adhesion molecules mediating cell-extracellular matrix interactions.
- Understanding integrin signaling, regulation, and structure-function relationships reveals therapeutic and diagnostic potential.
- Integrins play roles in various diseases, including cancer, cardiovascular, and inflammatory conditions.
Purpose of the Study:
- To review the critical role of alpha(v) integrins in tumor angiogenesis.
- To explore the potential of alpha(v) integrins in cancer diagnostics and therapy.
Main Methods:
- Literature review focusing on integrin research.
- Analysis of studies investigating alpha(v)beta(3) and alpha(v)beta(5) integrins in cancer.
Main Results:
- Alpha(v) integrins, specifically alpha(v)beta(3) and alpha(v)beta(5), are pivotal in tumor angiogenesis.
- Therapeutic candidates targeting integrins include antibodies, cyclic peptides, and peptidomimetics.
Conclusions:
- Alpha(v) integrins represent promising targets for anti-cancer diagnostics and therapeutics.
- Targeting tumor angiogenesis via alpha(v) integrins offers a potential strategy for cancer treatment.