ArticleOncogene2019
Combining CDK4/6 inhibition with taxanes enhances anti-tumor efficacy by sustained impairment of pRB-E2F pathways in squamous cell lung cancer.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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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.
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Who cites it
26 citing papers in PubMed, 44 citations in OpenAlex.
- CDK4-selective inhibitor AU2-94 for the treatment of advanced and therapy-resistant prostate cancer.Journal of experimental & clinical cancer research : CR · 2026Article
- A phase I study of the CDK4/6 inhibitor ribociclib combined with gemcitabine in patients with advanced solid tumors.BJC reports · 2025Article
- Circular RNAs and immunotherapy in retinoblastoma: emerging biomarkers and precision therapeutic strategies.Frontiers in immunology · 2025Review
- A Phase I Study of sequences of the CDK4/6 Inhibitor, Ribociclib Combined with Gemcitabine in Patients with Advanced Solid Tumors.Research square · 2024Article
- Circular RNAs: Regulators of endothelial cell dysfunction in atherosclerosis.Journal of molecular medicine (Berlin, Germany) · 2024Review
- CDK4/6 inhibitors in lung cancer: current practice and future directions.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Estrogen Therapy Induces Receptor-Dependent DNA Damage Enhanced by PARP Inhibition in ER+ Breast Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Mechanism of Taxanes in the Treatment of Lung Cancer Based on Network Pharmacology and Molecular Docking.Current issues in molecular biology · 2023Article
- CDK4/6 inhibition confers protection of normal gut epithelia against gemcitabine and the active metabolite of irinotecan.Cell cycle (Georgetown, Tex.) · 2023Article
- CDK4 and CDK6 kinases: From basic science to cancer therapy.Science (New York, N.Y.) · 2022Review
- Identification of kinases activated by multiple pro-angiogenic growth factors.Frontiers in pharmacology · 2022Article
- Combining a CDK4/6 Inhibitor With Pemetrexed Inhibits Cell Proliferation and Metastasis in Human Lung Adenocarcinoma.Frontiers in oncology · 2022Article
- Co-Adjuvant Therapy Efficacy of Catechin and Procyanidin B2 with Docetaxel on Hormone-Related Cancers In Vitro.International journal of molecular sciences · 2021Article
- Mechanisms and Implications of CDK4/6 Inhibitors for the Treatment of NSCLC.Frontiers in oncology · 2021Review
- Selective inhibition of CDK4/6: A safe and effective strategy for developing anticancer drugs.Acta pharmaceutica Sinica. B · 2021Review
- Bioinformatics analysis and experimental validation of TTK as a biomarker for prognosis in non-small cell lung cancer.Bioscience reports · 2020Article
- BET, SRC, and BCL2 family inhibitors are synergistic drug combinations with PARP inhibitors in ovarian cancer.EBioMedicine · 2020Article
- Identification of pathology-specific regulators of mThe EPMA journal · 2020Article
- Chemotherapy and CDK4/6 Inhibitors: Unexpected Bedfellows.Molecular cancer therapeutics · 2020Review
- Selective CDK4/6 Inhibitors: Biologic Outcomes, Determinants of Sensitivity, Mechanisms of Resistance, Combinatorial Approaches, and Pharmacodynamic Biomarkers.American Society of Clinical Oncology educational book. American Society of Clinical Oncology. Annual Meeting · 2020Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The CDK4/6 inhibitor palbociclib reduces tumor growth by decreasing retinoblastoma (RB) protein phosphorylation and inducing cell cycle arrest at the G1/S phase transition. Palbociclib in combination with anti-hormonal therapy brings significant benefit to breast cancer patients. In this study, novel combination approaches and underlying molecular/cellular mechanisms for palbociclib were explored in squamous cell lung cancer (SqCLC), the second most common subtype of non-small cell lung cancer. While approximate 20% lung patients benefit from immunotherapy, most SqCLC patients who receive platinum-doublet chemotherapy as first-line treatment, which often includes a taxane, are still in need of more effective combination therapies. Our results demonstrated enhanced cytotoxicity and anti-tumor effect with palbociclib plus taxanes at clinically achievable doses in multiple SqCLC models with diverse cancer genetic backgrounds. Comprehensive gene expression analysis revealed a sustained disruption of pRB-E2F signaling by combination that was accompanied with enhanced regulation of pleiotropic biological effects. These included several novel mechanisms such as abrogation of G2/M and mitotic spindle assembly checkpoints, as well as impaired induction of hypoxia-inducible factor 1 alpha (HIF-1α). The decrease in HIF-1α modulated a couple key angiogenic and anti-angiogenic factors, resulting in an enhanced anti-angiogenic effect. This preclinical work suggests a new therapeutic opportunity for palbociclib in lung and other cancers currently treated with taxane based chemotherapy as standard of care.
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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.