Purpose of Review Chronic myeloid leukemia (CML) patients with constitutive activity of BCR-ABL1 oncoprotein frequently derive significant clinical benefits from tyrosine kinase inhibitors (TKIs). Point mutations in the ABL1 kinase domain (KD) are an important mechanism of TKI resistance in CML. In...
In non-small cell lung cancer (NSCLC), several somatic mutations such as EGFR and EML4-ALK have been identified in a significant subgroup of patients. Multiple clinical trials involving tyrosine kinase inhibitors (TKIs) have demonstrated significant improvement in the prognosis of lung cancer patients...
Protein kinase inhibitors have applications as anticancer therapeutic agents and biological tools in cell signaling. Based on a phosphoryl transfer mechanism involving a dissociative transition state, a potent and selective bisubstrate inhibitor for the insulin receptor tyrosine kinase was synthesized by link...
novel targeted therapy including tyrosine-kinase inhibitors and immunotherapy are applied to cancer metastases. The process of metastasis is a multifaceted and inefficient phenomenon, encompassing various sequential steps and stochastic components.3,4It stands as the primary cause of cancer-related mortality...
These findings set constraints on the design of transition state analog inhibitors. Second, we describe efforts toward defining the specificity of Csk for peptide and protein substrates. The main findings are that local amino acids surrounding a phosphorylated tyrosine can influence recognition, but ...
Combination of a Proteomics Approach and Reengineering of Meso Scale Network Models for Prediction of Mode-of-Action for Tyrosine Kinase Inhibitors In drug discovery, the characterisation of the precise modes of action (MoA) and of unwanted off-target effects of novel molecularly targeted compounds is...
[193], EGFR tyrosine kinase inhibitors [194], and immunotherapy tolerance [195]. Intriguingly, autophagic flux can be driven by paclitaxel to promote paclitaxel resistance in ovarian cancer [196] and can be regulated by miR-30a [138], miR-200c [197], and miR-133a [198]. Furthermore, ...
Likewise, the use of tyrosine kinase inhibitors (TKIs) that target EGFR has not resulted in an increased survival among HNSCC patients. The modest effect of these drugs on overall survival in HNSCC patients may be a result of tumors becoming resistant to treatment in responding patients. Acquired...
Using cells engineered with inducible p16 we showed that Cyclin D/CDK4/6 activity was required for v-Src to increase expression of cyclin A but not cyclin E. To determine which downstream kinases mediated these effects of v-Src we added pharmacological inhibitors of phosphatidylinositol 3-kinase ...
We investigated a variety of angiogenesis inhibitors with different molecular targets including the small-molecule tyrosine kinase inhibitors sunitinib, vandetanib, pazopanib, axitinib, and sorafenib, the mammalian target of rapamycin (mTOR) inhibitor everolimus, the methionine aminopeptidase 2 (metAP2) inhib...