ArticleOncotarget2018
CDK4/6 inhibition stabilizes disease in patients with p16-null non-small cell lung cancer and is synergistic with mTOR inhibition.
Article in Oncotarget, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 1 of them a synthesis that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 1 synthesis or guideline pooled it, 47 citations in OpenAlex.
- Systematic literature review of real-world evidence for treatments in HR+/HER2- second-line LABC/mBC after first-line treatment with CDK4/6i.BMC cancer · 2024Pooled it
- Rewiring the Molecular Interplay of CDK4/6 Inhibitors in Lung Cancer: From Cell Cycle Control to Immune Microenvironment Remodeling.International journal of molecular sciences · 2026Review
- Alternate actions of CDK4/6 inhibitors beyond cell cycle blockade: unexplored roles in therapy resistance.Cancer metastasis reviews · 2025Review
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- Article
- SLAYER: a computational framework for identifying synthetic lethal interactions through integrated analysis of cancer dependencies.NAR genomics and bioinformatics · 2025Article
- Palbociclib as an Antitumor Drug: A License to Kill.Molecules (Basel, Switzerland) · 2024Review
- CDK4/6 inhibitors in lung cancer: current practice and future directions.European respiratory review : an official journal of the European Respiratory Society · 2024Review
- Bone metastasis in non-small-cell lung cancer: genomic characterization and exploration of potential targets.Therapeutic advances in medical oncology · 2024Article
- A landscape of response to drug combinations in non-small cell lung cancer.Nature communications · 2023Article
- Sequential Targeting of Retinoblastoma and DNA Synthesis Pathways Is a Therapeutic Strategy for Sarcomas That Can Be Monitored in Real Time.Cancer research · 2023Article
- Response to Abemaciclib and Immunotherapy Rechallenge with Nivolumab and Ipilimumab in a Heavily Pretreated TMB-H Metastatic Squamous Cell Lung Cancer with CDKN2A Mutation, PIK3CA Amplification and TPS 80%: A Case Report.International journal of molecular sciences · 2023Article
- CDC25C Protein Expression Correlates with Tumor Differentiation and Clinical Outcomes in Lung Adenocarcinoma.Biomedicines · 2023Article
- Molecular Mechanisms of Anti-Estrogen Therapy Resistance and Novel Targeted Therapies.Cancers · 2022Review
- Therapeutic potential of CDK4/6 inhibitors in renal cell carcinoma.Nature reviews. Urology · 2022Review
- Design and Synthesis of a Novel 4-aryl-N-(2-alkoxythieno [2,3-Pharmaceuticals (Basel, Switzerland) · 2022Article
- Gilteritinib Enhances Anti-Tumor Efficacy of CDK4/6 Inhibitor, Abemaciclib in Lung Cancer Cells.Frontiers in pharmacology · 2022Article
- Combining a CDK4/6 Inhibitor With Pemetrexed Inhibits Cell Proliferation and Metastasis in Human Lung Adenocarcinoma.Frontiers in oncology · 2022Article
- p27kip1 expression and phosphorylation dictate Palbociclib sensitivity in KRAS-mutated colorectal cancer.Cell death & disease · 2021Article
- The Role of Inherited Pathogenic CDKN2A Variants in Susceptibility to Pancreatic Cancer.Pancreas · 2021Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
Abstract
Aberrant activation of CDK4/6 kinase is the most common somatic event in non-small cell lung cancer (NSCLC). Palbociclib is a highly specific CDK4/6 inhibitor shown to inhibit cell cycle progression and promote cellular senescence. We conducted a phase 2 clinical trial of palbociclib in 19 previously-treated patients with advanced NSCLC. Only patients with p16-null staining by immunohistochemistry and documented tumor progression were eligible. The primary endpoint was tumor response rate. Palbociclib therapy alone was well-tolerated. Of 16 evaluable patients who received > 1 month of therapy, there were no objective responses. However, 8 patients (50%) with previously progressive NSCLC had stable disease (SD) lasting a range of 4-10.5 months. Median overall survival (OS) for all cases was 5.1 months, and median overall survival for the subset of patients with SD was 16.6 months. We also performed preclinical testing of palbociclib in combination with 13 different targeted or cytotoxic chemotherapeutic agents using a cell viability assay. Only the combination of palbociclib and mTOR inhibitors resulted in synergistic growth inhibition, particularly in tumors carrying RAS mutations. Our findings warrant further clinical investigation of the combination of palbociclib and mTOR inhibitors, especially in patients carrying activated RAS mutations.
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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.