ArticleCell cycle (Georgetown, Tex.)2017
The CDK4/6 inhibitor palbociclib synergizes with irinotecan to promote colorectal cancer cell death under hypoxia.
Article in Cell cycle (Georgetown, Tex.), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 46 citations in OpenAlex.
- CDK4/6-targeted therapy for gastrointestinal cancers: from resistance mechanisms to immuno-combination strategies guided by biomarkers.Frontiers in immunology · 2026Review
- Elucidating the Mechanisms of Acquired Palbociclib Resistance via Comprehensive Metabolomics Profiling.Current issues in molecular biology · 2025Article
- Article
- The search for CDK4/6 inhibitor biomarkers has been hampered by inappropriate proliferation assays.NPJ breast cancer · 2024Article
- Inhibition of epigenetic and cell cycle-related targets in glioblastoma cell lines reveals that onametostat reduces proliferation and viability in both normoxic and hypoxic conditions.Scientific reports · 2024Article
- Targeting the SMURF2-HIF1α axis: a new frontier in cancer therapy.Frontiers in oncology · 2024Review
- Preclinical evaluation of the CDK4/6 inhibitor palbociclib in combination with a PI3K or MEK inhibitor in colorectal cancer.Cancer biology & therapy · 2023Article
- Protective effects of palbociclib on colitis-associated colorectal cancer.Journal of gastrointestinal oncology · 2023Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- Inhibition of multiple CDKs potentiates colon cancer chemotherapy via p73-mediated DR5 induction.Oncogene · 2023Article
- Investigation on acquired palbociclib resistance by LC-MS based multi-omics analysis.Frontiers in molecular biosciences · 2023Article
- CDK4/6 Inhibition Suppresses p73 Phosphorylation and Activates DR5 to Potentiate Chemotherapy and Immune Checkpoint Blockade.Cancer research · 2022Article
- The Renaissance of Cyclin Dependent Kinase Inhibitors.Cancers · 2022Review
- Palbociclib induces cell senescence and apoptosis of gastric cancer cells by inhibiting the Notch pathway.Oncology letters · 2021Article
- Review
- Article
- An Update on the Potential Roles of E2F Family Members in Colorectal Cancer.Cancer management and research · 2021Review
- HSPA4 Knockdown Retarded Progression and Development of Colorectal Cancer.Cancer management and research · 2021Article
- A Precision Medicine Drug Discovery Pipeline Identifies Combined CDK2 and 9 Inhibition as a Novel Therapeutic Strategy in Colorectal Cancer.Molecular cancer therapeutics · 2020Article
- Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows.Molecular cancer therapeutics · 2020Review
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hypoxia is an inherent impediment to cancer therapy. Palbociclib, a highly selective inhibitor for CDK4/6, has been tested in numerous clinical trials and has been approved by the FDA. We previously reported that CDK inhibitors can destabilize HIF1α regardless of the presence of hypoxia and can sensitize tumor cells to TRAIL through dual blockade of CDK1 and GSK-3β. To translate this knowledge into a cancer therapeutic strategy, we investigated the therapeutic effects and molecular mechanisms of CDK inhibition against colon cancer cells under normoxia and hypoxia. We found that palbociclib sensitizes colon cancer cells to hypoxia-induced apoptotic resistance via deregulation of HIF-1α accumulation. In addition to inhibition of cell proliferation, we observed that palbociclib promotes colon cancer cell death regardless of the presence of hypoxia at a comparatively high concentration via regulating ERK/GSK-3β signaling and GSK-3β expression. Furthermore, palbociclib synergized with irinotecan in a variety of colon cancer cell lines with various molecular subtypes via deregulating irinotecan-induced Rb phosphorylation and reducing HIF-1α accumulation under normoxia or hypoxia. Collectively, our findings provide a novel combination therapy strategy against hypoxic colon cancer cells that may be further translated in the clinic.
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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.