ADAM proteases, ErbB pathways and cancer.
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.
Zhou
Bin-Bing S
BB
Drug Discovery Biology, Incyte Corporation, Experimental Station, Route 141 & Henry Clay Road, Building 400, Wilmington, DE 19880, USA. bzhou@incyte.com
Fridman
Jordan S
JS
Liu
Xiangdong
X
Friedman
Steve M
SM
Newton
Robert C
RC
Scherle
Peggy A
PA
D051722:ADAM Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D066246:ErbB Receptors / Q000037:antagonists & inhibitors* / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000502:physiology; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D066246:ErbB Receptors; D051722:ADAM Proteins