000190779 001__ 190779
000190779 005__ 20190316235749.0
000190779 0247_ $$2doi$$a10.1177/1947601912458584
000190779 022__ $$a1947-6019
000190779 037__ $$aARTICLE
000190779 245__ $$aStructure, regulation, signaling, and targeting of abl kinases in cancer
000190779 269__ $$a2012
000190779 260__ $$c2012
000190779 336__ $$aJournal Articles
000190779 520__ $$aAbl kinases are prototypic cytoplasmic tyrosine kinases and are involved in a variety of chromosomal aberrations in different cancers. This causes the expression of Abl fusion proteins, such as Bcr-Abl, that are constitutively activated and drivers of tumorigenesis. Over the past decades, biochemical and functional studies on the molecular mechanisms of Abl regulation have gone hand in hand with progression of our structural understanding of autoinhibited and active Abl conformations. In parallel, Abl oncoproteins have become prime molecular targets for cancer therapy, using adenosine triphosphate (ATP)-competitive kinase inhibitors, such as imatinib. Abl-targeting drugs serve as a paradigm for our understanding of kinase inhibitor action, specificity, and resistance development. In this review article, I will review the molecular mechanisms that are responsible for the regulation of Abl kinase activity and how oncogenic Abl fusions signal. Furthermore, past and ongoing efforts to target Abl oncoproteins using ATP-competitive and allosteric inhibitors, as well as future possibilities using combination therapy, will be discussed.
000190779 700__ $$g209845$$0245280$$aHantschel, Oliver
000190779 773__ $$j3$$tGenes & cancer$$k5-6$$q436-46
000190779 8564_ $$uhttps://infoscience.epfl.ch/record/190779/files/10.1177_1947601912458584.pdf$$zPublisher's version$$s4817856$$yPublisher's version
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000190779 917Z8 $$x182396
000190779 937__ $$aEPFL-ARTICLE-190779
000190779 973__ $$rREVIEWED$$sPUBLISHED$$aEPFL
000190779 980__ $$aARTICLE