Not exact matches
They found that CD44 + / CD24 - / Low cancer stem cells (CSCs) were resistant to conventional chemotherapy but were sensitive to SU9516, which is a
specific cyclin - dependent
kinase 2 (Cdk2)
inhibitor.
The drug is a multi -
kinase inhibitor (MKI)-- meaning it targets the
specific enzymes that are required for growth in DTC.
Another focus was the differential sensitivity of different mutations towards inhibition with
specific tyrosine
kinase inhibitors (5).
Here we use a chemical genetics approach using knock - in mice in which either p38alpha or p38beta
kinase has been rendered resistant to the effects of
specific inhibitors along with p38beta knock - out mice to dissect the biological function of these
specific kinase isoforms.
The allosteric
inhibitors specific for ABL
kinases (which are currently in clinical trials) provide a potentially useful tool for selectively targeting ABL
kinases in metastatic breast cancer types with an increase in the ABL pathway signature (58).
These mutant
kinases are attractive therapeutic targets, as demonstrated by the efficacy of imatinib in BCR - ABL — positive chronic myelogenous leukemia (CML), 5 as well as in MPD associated with activating alleles involving PDGFRA or PDGFRB.2, 6,7 In addition, activating mutations in the FLT3 receptor tyrosine
kinase are the most common genetic event in acute myeloid leukemia (AML), and
specific inhibitors of the FMS - like tyrosine
kinase 3 (FLT3) have entered late - stage clinical trials.8 Although mutations in tyrosine
kinases and in other genes have been identified in a subset of MPD and AML, in many cases the genetic events that contribute to the molecular pathogenesis of these diseases remain unknown.
This signal can effectively be inhibited using RIPK2
inhibitors 1 and 2 and regorafenib (a known RIPK2
kinase inhibitor) at 100 nM as determined using RIPK2 phospho -
specific antibodies (Fig. 4, A and B).
Insofar as
kinase inhibitors interfere with signaling dynamics, and, in turn, signaling dynamics affects
inhibitor responses, we investigated associations in this study between cell -
specific dynamic signaling pathways and drug sensitivity.
In contrast, loss of adhesion induced the phosphatases Dusp4 and -5 (Map -
kinase phosphatases), which are
inhibitors of the MAP -
kinase signaling pathway, whereas contact inhibition induced the quiescent cell -
specific transcription
inhibitor E2F4.