ArticleOncotarget2020
Combined inhibition of PIM and CDK4/6 suppresses both mTOR signaling and Rb phosphorylation and potentiates PI3K inhibition in cancer cells.
Article in Oncotarget, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Combined inhibition of CDK4/6 and PI3K pathways exhibit highly synergistic activity and translational potential in Ewing sarcoma.Translational oncology · 2026Article
- The search for CDK4/6 inhibitor biomarkers has been hampered by inappropriate proliferation assays.NPJ breast cancer · 2024Article
- Lipid-lowering drugs and cancer: an updated perspective.Pharmacological reports : PR · 2024Review
- The Evolving Pathways of the Efficacy of and Resistance to CDK4/6 Inhibitors in Breast Cancer.Cancers · 2023Review
- Phosphoinositide 3-Kinase (PI3K) Inhibitors and Breast Cancer: An Overview of Current Achievements.Cancers · 2023Review
- Targeting mTOR to overcome resistance to hormone and CDK4/6 inhibitors in ER-positive breast cancer models.Scientific reports · 2023Article
- Combined inhibition of ACLY and CDK4/6 reduces cancer cell growth and invasion.Oncology reports · 2023Article
- CDK4/6 Inhibition Enhances the Efficacy of Standard Chemotherapy Treatment in Malignant Pleural Mesothelioma Cells.Cancers · 2022Article
- Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib.The oncologist · 2022Review
- Targeting CDK4 and CDK6 in cancer.Nature reviews. Cancer · 2022Review
- Cellular mechanisms underlying response and resistance to CDK4/6 inhibitors in the treatment of hormone receptor-positive breast cancer.Breast cancer research : BCR · 2022Review
- Interpretable deep recommender system model for prediction of kinase inhibitor efficacy across cancer cell lines.Scientific reports · 2021Article
- ERK Inhibitor LY3214996-Based Treatment Strategies forMolecular cancer therapeutics · 2021Article
- Breast Cancer Resistance to Cyclin-Dependent Kinases 4/6 Inhibitors: Intricacy of the Molecular Mechanisms.Frontiers in oncology · 2021Review
- Potential synergism of abemaciclib with chloroquine and disulfiram/copper in atypical meningioma: A case report and review of the literature.Neuro-oncology advancesArticle
Corrections and comments
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Authors and funding
16 authors at 3 institutions in 3 countries.
Funding
Abstract
Aberrant activation of mitogenic signaling pathways in cancer promotes growth and proliferation of cells by activating mTOR and S6 phosphorylation, and D-cyclin kinases and Rb phosphorylation, respectively. Correspondingly, inhibition of phosphorylation of both Rb and S6 is required for robust anti-tumor efficacy of drugs that inhibit cell signaling. The best-established mechanism of mTOR activation in cancer is via PI3K/Akt signaling, but mTOR activity can also be stimulated by CDK4 and PIM kinases. In this study, we show that the CDK4/6 inhibitor abemaciclib inhibits PIM kinase and S6 phosphorylation in cancer cells and concurrent inhibition of PIM, CDK4, and CDK6 suppresses both S6 and Rb phosphorylation.
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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.