IMR Press / FBE / Volume 3 / Issue 3 / DOI: 10.2741/E287

Frontiers in Bioscience-Elite (FBE) is published by IMR Press from Volume 13 Issue 2 (2021). Previous articles were published by another publisher on a subscription basis, and they are hosted by IMR Press on imrpress.com as a courtesy and upon agreement with Frontiers in Bioscience.

Open Access Article
Src-family tyrosine kinases as therapeutic targets in advanced cancer
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1 Department of Cancer Genetics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY

*Author to whom correspondence should be addressed.

Academic Editor: Irwin H. Gelman

Front. Biosci. (Elite Ed) 2011, 3(3), 801–807; https://doi.org/10.2741/E287
Published: 1 June 2011
(This article belongs to the Special Issue Scaffolding proteins as regulators of signaling)
Abstract

Src-family tyrosine kinases (SFK) play critical roles in mediating many cellular pathways such as proliferation, adhesion, survival, differentiation and cell motility. There is clear evidence that SFK activity is increased in many human cancers, either through gene amplification, transcriptional upregulation, posttranslational modification by activated upstream growth factor receptors, and even in rare cases, by mutations known to increase intrinsic tyrosine kinase activity in oncoviral forms of SFK. Many recent studies using animal models of human cancer seem to indicate that SFK may only be appropriate therapeutic targets in a subset of primary tumors because of the existence of multiple independent pathways that mediate oncogenic signaling. In contrast, SFK seem to be required for specific parameters of malignant progression, such as recurrence and/or metastasis- especially involving growth in the bone microenvironment. The resulting development of SFK antagonists, and their progression through clinical trials, has brought renewed focus on this tyrosine kinase family as critical mediators of the so-called lethal phenotype of cancer.

Keywords
Src-family kinases
Src
Yes
Fyn
Blk
Fgr
Hck
Lck
Lyn
Yrk
Frk
cancer recurrence
metastasis
tyrosine kinase
chemotherapy resistance
osteoclasts
RANKL-osteoprotegerin
SSeCKS
Gravin
AKAP12
VEGF
tumor microenvironment
IGF-1
Dasatinib
BMS354825
Sprycel
Bosutinib
SKI-606
Saracatinib
AZD0530
PD180970
SU6656
KXO1
KX2-391
CGP76030
AP23451
AZM475271
INNO-406
NS-187
XL-999
XL-228
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