ArticleCancer research2015
Activation of Pim Kinases Is Sufficient to Promote Resistance to MET Small-Molecule Inhibitors.
Article in Cancer research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
18 citing papers in PubMed, 25 citations in OpenAlex.
- 7-azaindole as privileged scaffold: Advances in drug design and structural modification.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Review
- PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.Nature communications · 2025Article
- Role of guanylate-binding protein 1 in the proliferation of invasive lung adenocarcinoma cells.Frontiers in oncology · 2025Article
- PIM3 Kinase: A Promising Novel Target in Solid Cancers.Cancers · 2024Review
- Biological insights in non-small cell lung cancer.Cancer biology & medicine · 2023Review
- Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.Cancers · 2021Article
- A narrative review of MET inhibitors in non-small cell lung cancer withTranslational lung cancer research · 2021Review
- SRC and PIM1 as potential co-targets to overcome resistance in MET deregulated non-small cell lung cancer.Translational lung cancer research · 2020Article
- Human papillomavirus insertions identify the PIM family of serine/threonine kinases as targetable driver genes in head and neck squamous cell carcinoma.Cancer letters · 2020Article
- Combined inhibition of PIM and CDK4/6 suppresses both mTOR signaling and Rb phosphorylation and potentiates PI3K inhibition in cancer cells.Oncotarget · 2020Article
- Targeting the HGF/MET Axis in Cancer Therapy: Challenges in Resistance and Opportunities for Improvement.Frontiers in cell and developmental biology · 2020Review
- A review on PIM kinases in tumors.Bioinformation · 2019Article
- Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase.Molecular cancer therapeutics · 2018Article
- Microenvironment-induced PIM kinases promote CXCR4-triggered mTOR pathway required for chronic lymphocytic leukaemia cell migration.Journal of cellular and molecular medicine · 2018Article
- PIM2 interacts with tristetraprolin and promotes breast cancer tumorigenesis.Molecular oncology · 2018Article
- Bcl-2 and Bcl-xL mediate resistance to receptor tyrosine kinase-targeted therapy in lung and gastric cancer.Anti-cancer drugs · 2017Article
- ZNF32 contributes to the induction of multidrug resistance by regulating TGF-β receptor 2 signaling in lung adenocarcinoma.Cell death & disease · 2016Article
- Acquired savolitinib resistance in non-small cell lung cancer arises via multiple mechanisms that converge on MET-independent mTOR and MYC activation.Oncotarget · 2016Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
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 MET amplification. Inhibition of Pim kinases enhanced cell death triggered by short-term treatment with MET inhibitors. Pim kinases control the translation of antiapoptotic protein Bcl-2 at an internal ribosome entry site and this mechanism was identified as the basis for Pim-mediated resistance to MET inhibitors. Protein synthesis was increased in drug-resistant cells, secondary to a Pim-mediated increase in cap-independent translation. In cells rendered drug resistant by chronic treatment with MET inhibitors, genetic or pharmacologic inhibition of Pim kinases was sufficient to restore sensitivity in vitro and in vivo. Taken together, our results rationalize Pim inhibition as a strategy to augment responses and blunt acquired resistance to MET inhibitors in cancer.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.