Publication: c-KIT signaling as the driving oncogenic event in sub-groups of melanomas
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Date
2009
Authors
Smalley, Keiran S.M. ; Sondak, Vernon K. ; Weber, Jeffrey S.
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Publisher
Murcia : F. Hernández
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DOI
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info:eu-repo/semantics/article
Description
Abstract
As we enter the era of targeted therapy for
melanoma, attempts are being made to sub-group tumors
on the basis of their driving oncogenic mutations, with
the hope of developing truly personalized therapeutic
regimens. c-KIT is a receptor tyrosine kinase whose
aberrant activation is implicated in the progression of
gastrointestinal stromal tumors and some acute myeloid
leukemias. The role of c-KIT signaling in melanoma has
been controversial; although c-KIT activity is critical to
melanocyte development, its expression tends to be lost
in most melanomas. Some reports have even shown that
the re-expression of c-KIT induces apoptosis in
melanoma cell lines.
The recent publication of work showing the presence
of activating c-KIT mutations in acral and mucosal
melanomas, as well as melanomas arising on skin with
chronic sun damage, has renewed interest in c-KIT
signaling in melanoma. Recent work from our own
laboratory has further identified melanomas with
constitutive c-KIT signaling activity resulting from c-
KIT receptor overexpression. Although the initial
clinical trials of the c-KIT inhibitor imatinib mesylate in
melanoma were negative, some dramatic responses have
been seen in patients with very high c-KIT expression
and/or documented activating mutations, fostering the
belief that focused studies in patients selected on the
basis of c-KIT mutational status will yield more
encouraging results. The current review discusses the
role of c-KIT signaling in melanoma progression and
how this new information can be applied to the targeted
therapy of melanoma.
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