ArticleMolecular cancer therapeutics2018
Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase.
Article in Molecular cancer therapeutics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 48 citations in OpenAlex.
- Article
- RBM19 promotes the progression of prostate cancer under docetaxel treatment via SNHG21/PIM1 axis.Cell biology and toxicology · 2024Article
- Resistance to Targeted Inhibitors of the PI3K/AKT/mTOR Pathway in Advanced Oestrogen-Receptor-Positive Breast Cancer.Cancers · 2024Review
- PIM1 drives lipid droplet accumulation to promote proliferation and survival in prostate cancer.Oncogene · 2024Article
- Mutant PIK3CA as a negative predictive biomarker for treatment with a highly selective PIM1 inhibitor in human colon cancer.Cancer biology & therapy · 2023Article
- Prostate cancer immunotherapy: Improving clinical outcomes with a multi-pronged approach.Cell reports. Medicine · 2023Review
- An overview of pim kinase as a target in multiple myeloma.Cancer medicine · 2023Review
- Phosphoinositide 3-Kinase (PI3K) Inhibitors and Breast Cancer: An Overview of Current Achievements.Cancers · 2023Review
- PIM1 promotes hepatic conversion by suppressing reprogramming-induced ferroptosis and cell cycle arrest.Nature communications · 2022Article
- Synthesis of 2-Oxoquinoline Derivatives as Dual Pim and mTORC Protein Kinase Inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2022Article
- Synergistic PIM kinase and proteasome inhibition as a therapeutic strategy for MYC-overexpressing triple-negative breast cancer.Cell chemical biology · 2022Article
- The long noncoding RNA H19 regulates tumor plasticity in neuroendocrine prostate cancer.Nature communications · 2021Article
- Co-Targeting PIM Kinase and PI3K/mTOR in NSCLC.Cancers · 2021Article
- EDC3 phosphorylation regulates growth and invasion through controlling P-body formation and dynamics.EMBO reports · 2021Article
- PI3K Inhibitors in Cancer: Clinical Implications and Adverse Effects.International journal of molecular sciences · 2021Review
- Targeting PI3K/Akt/mTOR in AML: Rationale and Clinical Evidence.Journal of clinical medicine · 2020Review
- Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer.Scientific reports · 2020Article
- PIM protein kinases regulate the level of the long noncoding RNA H19 to control stem cell gene transcription and modulate tumor growth.Molecular oncology · 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
- PIM1 inhibitor synergizes the anti-tumor effect of osimertinib via STAT3 dephosphorylation in EGFR-mutant non-small cell lung cancer.Annals of translational medicine · 2020Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
Cancer resistance to PI3K inhibitor therapy can be in part mediated by increases in the PIM1 kinase. However, the exact mechanism by which PIM kinase promotes tumor cell resistance is unknown. Our study unveils the pivotal control of redox signaling by PIM kinases as a driver of this resistance mechanism. PIM1 kinase functions to decrease cellular ROS levels by enhancing nuclear factor erythroid 2-related factor 2 (NRF2)/antioxidant response element activity. PIM prevents cell death induced by PI3K-AKT-inhibitory drugs through a noncanonical mechanism of NRF2 ubiquitination and degradation and translational control of NRF2 protein levels through modulation of eIF4B and mTORC1 activity. Importantly, PIM also 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. Treatment with PIM kinase inhibitors reverses this resistance phenotype, making tumors increasingly susceptible to small-molecule therapeutics, which block the PI3K-AKT pathway.
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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.