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Title: Receptor tyrosine kinases and their activation in melanoma.
Author: O'BYRNE, KEN
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Keywords: Oncology
Receptor tyrosine kinases (RTKs)
Issue Date: 2011
Publisher: Wiley
Citation: Easty DJ, Gray SG, O'Byrne KJ, O'Donnell D, Bennett DC, Receptor tyrosine kinases and their activation in melanoma., Pigment Cell & Melanoma Research, 24, 3, 2011, 446 461
Series/Report no.: Pigment Cell & Melanoma Research;
Abstract: Receptor tyrosine kinases (RTKs) and their downstream signalling pathways have long been hypothesized to play key roles in melanoma development. A decade ago, evidence was derived largely from animal models, RTK expression studies and detection of activated RAS isoforms in a small fraction of melanomas. Predictions that overexpression of specific RTKs implied increased kinase activity and that some RTKs would show activating mutations in melanoma were largely untested. However, technological advances including rapid gene sequencing, siRNA methods and phospho-RTK arrays now give a more complete picture. Mutated forms of RTK genes including KIT, ERBB4, the EPH and FGFR families and others are known in melanoma. Additional over- or underexpressed RTKs and also protein tyrosine phosphatases (PTPs) have been reported, and activities measured. Complex interactions between RTKs and PTPs are implicated in the abnormal signalling driving aberrant growth and survival in malignant melanocytes, and indeed in normal melanocytic signalling including the response to ultraviolet radiation. Kinases are considered druggable targets, so characterisation of global RTK activity in melanoma should assist the rational development of tyrosine kinase inhibitors for clinical use.
Description: PUBLISHED
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Appears in Collections:Clinical Medicine (Scholarly Publications)

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