ArticleCancer research2012
Pim kinase inhibitors sensitize prostate cancer cells to apoptosis triggered by Bcl-2 family inhibitor ABT-737.
Article in Cancer research, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 59 citations in OpenAlex.
- FromRSC advances · 2026Article
- PIM2 inhibition promotes MCL1 dependency in plasma cells involving integrated stress response-driven NOXA expression.Nature communications · 2025Article
- Role of NuMA1 in breast cancer stem cells with implications for combination therapy of PIM1 and autophagy inhibition in triple negative breast cancer.Research square · 2024Article
- The endoplasmic reticulum stress response in prostate cancer.Nature reviews. Urology · 2022Review
- PPAR agonists attenuate lenalidomide's anti-myeloma activity in vitro and in vivo.Cancer letters · 2022Article
- IBL-202 is synergistic with venetoclax in CLL under in vitro conditions that mimic the tumor microenvironment.Blood advances · 2020Article
- Preclinical evaluation of a novel triple-acting PIM/PI3K/mTOR inhibitor, IBL-302, in breast cancer.Oncogene · 2020Article
- Small-Molecule-Targeting Hairpin Loop of hTERT Promoter G-Quadruplex Induces Cancer Cell Death.Cell chemical biology · 2019Article
- Pan-PIM kinase inhibitors enhance Lenalidomide's anti-myeloma activity via cereblon-IKZF1/3 cascade.Cancer letters · 2019Article
- Mechanisms Behind Resistance to PI3K Inhibitor Treatment Induced by the PIM Kinase.Molecular cancer therapeutics · 2018Article
- Corosolic acid, a natural triterpenoid, induces ER stress-dependent apoptosis in human castration resistant prostate cancer cells via activation of IRE-1/JNK, PERK/CHOP and TRIB3.Journal of experimental & clinical cancer research : CR · 2018Article
- PIM-2 protein kinase negatively regulates T cell responses in transplantation and tumor immunity.The Journal of clinical investigation · 2018Article
- Glycycoumarin Sensitizes Liver Cancer Cells to ABT-737 by Targeting De Novo Lipogenesis and TOPK-Survivin Axis.Nutrients · 2018Article
- Synergistic cytotoxicity of a prostate cancer-specific immunotoxin in combination with the BH3 mimetic ABT-737.Cancer immunology, immunotherapy : CII · 2018Article
- Concurrent Inhibition of Pim and FLT3 Kinases Enhances Apoptosis of FLT3-ITD Acute Myeloid Leukemia Cells through Increased Mcl-1 Proteasomal Degradation.Clinical cancer research : an official journal of the American Association for Cancer Research · 2018Article
- BH3 Mimetics for the Treatment of Prostate Cancer.Frontiers in pharmacology · 2017Article
- Prostate cancer and the unfolded protein response.Oncotarget · 2016Review
- Intrinsic resistance to PIM kinase inhibition in AML through p38α-mediated feedback activation of mTOR signaling.Oncotarget · 2016Article
- Article
- Combination of Pim kinase inhibitors and Bcl-2 antagonists in chronic lymphocytic leukemia cells.Leukemia & lymphoma · 2016Article
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
Pim serine/threonine kinases contribute to prostate tumorigenesis and therapeutic resistance, yet Pim kinase inhibitors seem to have only limited effects on prostate cancer cell survival. Because overexpression of Bcl-2 family members are implicated in chemotherapeutic resistance in prostate cancer, we investigated the cooperative effects of Pim kinase inhibition with ABT-737, a small molecule antagonist of Bcl-2 family members. Strikingly, the addition of ABT-737 to Pim inhibitors triggered a robust apoptosis of prostate cancer cells in vitro and in vivo. Pim inhibitors decreased levels of the Bcl-2 family member Mcl-1, both by blocking 5'-cap dependent translation and decreasing protein half life. In addition, Pim inhibition transcriptionally increased levels of the BH3 protein Noxa by activating the unfolded protein response (UPR), lead to eIF-2α phosphorylation and increased expression of CHOP. Increased levels of Noxa also inactivated the remaining levels of Mcl-1 protein activity. Notably, these specific protein changes were essential to the apoptotic process because ABT-737 did not inhibit Mcl-1 protein activity and Mcl-1 overexpression blocked the apoptotic activity of ABT-737. Our results therefore suggest that this combination treatment could be developed as a potential therapy for human prostate cancer where overexpression of Pim kinases and antiapoptotic Bcl-2 family members drives tumor cell resistance to current anticancer therapies.
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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.