Activation of Pim Kinases Is Sufficient to Promote Resistance to MET Small-Molecule Inhibitors.

@article{An2015ActivationOP,
  title={Activation of Pim Kinases Is Sufficient to Promote Resistance to MET Small-Molecule Inhibitors.},
  author={Ningfei An and Ying Xiong and Amanda C. Larue and Andrew S. Kraft and Bo Cen},
  journal={Cancer research},
  year={2015},
  volume={75 24},
  pages={
          5318-28
        }
}
Mesenchymal-epithelial transition (MET) blockade offers a new targeted therapy particularly in those cancers with MET amplification. However, the efficacy and the duration of the response to MET inhibitors are limited by the emergence of drug resistance. Here, we report that resistance to small-molecule inhibitors of MET can arise from increased expression of the prosurvival Pim protein kinases. This resistance mechanism was documented in non-small cell lung cancer and gastric cancer cells with… 
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SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer.
TLDR
A potential role of PIM inhibition inMET amplified tumors and of SRC inhibition in MET addicted tumors is identified and potential applications of this new treatment strategy warrant further evaluation.
Current perspectives on targeting PIM kinases to overcome mechanisms of drug resistance and immune evasion in cancer.
Overcoming Resistance to Inhibitors of the Akt Protein Kinase by Modulation of the Pim Kinase Pathway
TLDR
It is demonstrated that resistance to small molecule AKTprotein kinase inhibitors is potentially mediated by the Pim-1 protein kinase, and that unique Pim protein kinases that can in turn synergize with AKT inhibitors to block prostate cancer growth overcome this resistance.
Targeting PIM Kinases to Overcome Therapeutic Resistance in Cancer
TLDR
This review focuses on the signaling pathways through which PIM kinases promote cancer progression and resistance to therapy, as well as highlights biological contexts and promising strategies to exploit PIM as a therapeutic target in cancer.
Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase
TLDR
PIM controls NAD(P)H production by increasing glucose flux through the pentose phosphate shunt decreasing ROS production, and thereby diminishing the cytotoxicity of PI3K-AKT inhibitors.
Targeting the HGF/MET Axis in Cancer Therapy: Challenges in Resistance and Opportunities for Improvement
TLDR
A review of the current challenges and future opportunities for HGF/MET targeting for therapeutic cancer interventions is summarized and simultaneously proposed.
A review on PIM kinases in tumors
TLDR
As Pim-1 possesses oncogenic functions and is over expressed in various kinds of cancer diseases, its inhibition provides a new option in cancer therapy and designing new inhibitors of PIMs is now a very active area of research in academic and industrial laboratories.
Bcl-2 and Bcl-xL mediate resistance to receptor tyrosine kinase-targeted therapy in lung and gastric cancer
TLDR
A generalizable resistance mechanism to TKIs is defined and inhibition of B cl-2 and Bcl-xL is rationalized as a strategy to augment responses and blunt acquired resistance to TkIs in lung and gastric cancer.
A narrative review of MET inhibitors in non-small cell lung cancer with MET exon 14 skipping mutations.
TLDR
This review discusses the role and setting for use of selective MET inhibitors, mainly focusing on selective MET tyrosine kinase inhibitors (TKIs), in the treatment of NSCLC with MET exon 14 skipping mutations.
MET receptor in oncology: From biomarker to therapeutic target.
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