ArticleThoracic cancer2020
CDK4/6 inhibitor palbociclib overcomes acquired resistance to third-generation EGFR inhibitor osimertinib in non-small cell lung cancer (NSCLC).
Article in Thoracic cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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Who cites it
33 citing papers in PubMed, 46 citations in OpenAlex.
- Oncogenic mutations in non-small cell lung cancer: from molecular mechanisms to clinical practice.Signal transduction and targeted therapy · 2026Review
- HES1 inhibition overcomes CDK4/6 inhibitor resistance by targeting cancer stemness in lung adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- The changing treatment landscape of EGFR-mutant non-small-cell lung cancer.Nature reviews. Clinical oncology · 2025Review
- Optimizing Osimertinib for NSCLC: Targeting Resistance and Exploring Combination Therapeutics.Cancers · 2025Review
- Ethyl acetate extract ofFrontiers in pharmacology · 2025Article
- CDK4/6 inhibitors in lung cancer: current practice and future directions.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Strategy of combining CDK4/6 inhibitors with other therapies and mechanisms of resistance.International journal of clinical and experimental pathology · 2024Review
- Dual network analysis of transcriptome data for discovery of new therapeutic targets in non-small cell lung cancer.Oncogene · 2023Article
- CDK4/6 signaling attenuates the effect of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors inTranslational lung cancer research · 2023Article
- New insights into the biology and development of lung cancer in never smokers-implications for early detection and treatment.Journal of translational medicine · 2023Review
- The Resistance to EGFR-TKIs in Non-Small Cell Lung Cancer: From Molecular Mechanisms to Clinical Application of New Therapeutic Strategies.Pharmaceutics · 2023Review
- 3-Phosphoinositide-dependent kinase 1 drives acquired resistance to osimertinib.Communications biology · 2023Article
- Precision targeted therapy for EGFR mutation-positive NSCLC: Dilemmas and coping strategies.Thoracic cancer · 2023Review
- Review
- Identification of afatinib-associated ADH1B and potential small-molecule drugs targeting ADH1B for hepatocellular carcinoma.Frontiers in pharmacology · 2023Article
- Therapeutic strategies for EGFR-mutated non-small cell lung cancer patients with osimertinib resistance.Journal of hematology & oncology · 2022Review
- A review on the role of cyclin dependent kinases in cancers.Cancer cell international · 2022Review
- Targeting CDK4 and 6 in Cancer Therapy: Emerging Preclinical Insights Related to Abemaciclib.The oncologist · 2022Review
- Resistance to TKIs in EGFR-Mutated Non-Small Cell Lung Cancer: From Mechanisms to New Therapeutic Strategies.Cancers · 2022Review
- Acquired Resistance to Osimertinib inInternational journal of molecular sciences · 2022Review
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe third-generation EGFR-TKI, represented by osimertinib, has been widely used in clinical practice; however, resistance eventually emerges. At present, it remains unclear whether an abnormal cell cycle is involved in acquired resistance, and whether the combination of palbociclib (CDK4/6 inhibitor) and osimertinib can overcome the third-generation TKI resistance.
methodsWe established osimertinib-resistant cells (H1975 OR) derived from EGFR-mutant NSCLC cells H1975. Drug effects on cells were assessed with Cell Counting Kit-8 (CCK8). Protein alterations were detected with western blot analysis. RT-PCR was used to evaluate the differences of gene mRNA. Cell cycle distribution of H1975 S and H1975 OR cells was compared using flow cytometry.
resultsCompared with H1975, the sensitivity of H1975OR to the CDK4/6 inhibitor was increased and the proportion of cells in G1 phase was decreased. The mRNA level of CDK4, CDK 6 and the protein level of CDK4, pRB were increased in H1975OR. In the H1975OR cells, palbociclib significantly increased the proportion of G1 phase cells. The combination of osimertinib and palbociclib synergistically decreased the survival of H1975OR by cell cycle arrest. Combined treatment was found to inhibit the initial phosphorylation of RB by inhibiting the function of CDK4/6, significantly reducing the level of p-RB, and blocking cell proliferation.
conclusionsAn osimertinib acquired resistance cell line (H1975 OR) was successfully established. The expression of cell cycle related genes was altered in H1975OR. The expression of CDK4 and the phosphorylation of Rb, the downstream molecule of CDK4/6, was increased in H1975OR cells. The combination of CDK4/6 inhibitor palbociclib and osimertinib could overcome the acquired resistance of osimertinib.
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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.