Abstract
A disintegrin and metalloproteases (ADAMs) are zinc-dependent trans-membrane metalloproteases that shed the extracellular domains of membrane-bound growth factors, cytokines and receptors. Key functions of ADAMs have emerged in ErbB signalling pathways as being sheddases for multiple ErbB ligands. As the ErbB pathway is a validated target for anti-cancer drugs, the upstream activators of ErbB ligands, their sheddases, now enter the spotlight as new drug targets in the ErbB pathway. ADAMs are involved not only in tumour cell proliferation but also in angiogenesis and metastasis. Therefore, strategies targeting ADAMs might be an important complement to existing anti-ErbB approaches.
MeSH terms
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ADAM Proteins / antagonists & inhibitors*
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ADAM Proteins / metabolism
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Animals
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Antineoplastic Agents / chemistry
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Antineoplastic Agents / pharmacology
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Antineoplastic Agents / therapeutic use*
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Enzyme Inhibitors / chemistry
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Enzyme Inhibitors / pharmacology
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Enzyme Inhibitors / therapeutic use
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ErbB Receptors / antagonists & inhibitors*
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ErbB Receptors / metabolism
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Gene Expression Regulation, Neoplastic / drug effects
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Gene Expression Regulation, Neoplastic / physiology
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Humans
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Neoplasms / drug therapy
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Neoplasms / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology*
Substances
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Antineoplastic Agents
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Enzyme Inhibitors
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ErbB Receptors
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ADAM Proteins