ArticleThe Annals of thoracic surgery2022
Inhibition of Cyclin Dependent Kinase 4/6 Overcomes Primary Resistance to Programmed Cell Death 1 Blockade in Malignant Mesothelioma.
Article in The Annals of thoracic surgery, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- Ad-SGE-DKK3 Gene Therapy Overcomes Resistance to Immune Checkpoint Blockade in Pleural Mesothelioma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2025Trial
- Moving Beyond Morphology: Toward a Morpho-Molecular Classification of Pleural Mesothelioma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Review
- Regional immunosuppression and associated systemic markers in focally relapsed sarcomatoid mesothelioma: case report.Journal for immunotherapy of cancer · 2026Article
- CDKN2A deletion is associated with immune desertification in diffuse pleural mesothelioma.Journal of experimental & clinical cancer research : CR · 2025Article
- The regulatory role of CDK4/6 inhibitors in tumor immunity and the potential value of tumor immunotherapy (Review).International journal of molecular medicine · 2025Review
- Soluble mesothelin-related peptide as a prognosticator in pleural mesothelioma patients receiving checkpoint immunotherapy.The Journal of thoracic and cardiovascular surgery · 2025Article
- A CDKN2B-Associated Immune Prognostic Model for Predicting Immune Cell Infiltration and Prognosis in Esophageal Carcinoma.Clinical and experimental gastroenterology · 2025Article
- LKB1 dictates sensitivity to immunotherapy through Skp2-mediated ubiquitination of PD-L1 protein in non-small cell lung cancer.Journal for immunotherapy of cancer · 2024Article
- Preclinical evaluation of CDK4 phosphorylation predicts high sensitivity of pleural mesotheliomas to CDK4/6 inhibition.Molecular oncology · 2024Article
- Pharmacological inhibition of CDK4/6 impairs diffuse pleural mesothelioma 3D spheroid growth and reduces viability of cisplatin-resistant cells.Frontiers in oncology · 2024Article
- Genomic Landscape of Pleural Mesothelioma and Therapeutic Aftermaths.Current oncology reports · 2023Review
- Immune Checkpoint Therapy Combinations in Adult Advanced MiT Family Translocation Renal Cell Carcinomas.The oncologist · 2023Article
- A Selective ALDH1A3 Inhibitor Impairs Mesothelioma 3-D Multicellular Spheroid Growth and Neutrophil Recruitment.International journal of molecular sciences · 2023Article
- Review
- The mechanism and clinical application of DNA damage repair inhibitors combined with immune checkpoint inhibitors in the treatment of urologic cancer.Frontiers in cell and developmental biology · 2023Review
- Applications and mechanisms of the cyclin-dependent kinase 4/6 inhibitor, PD-0332991, in solid tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- IsolatedCancers · 2022Article
- The Rocky Road from Preclinical Findings to Successful Targeted Therapy in Pleural Mesothelioma.International journal of molecular sciences · 2022Review
- A Glimpse in the Future of Malignant Mesothelioma Treatment.Frontiers in pharmacology · 2021Review
Corrections and comments
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Authors and funding
12 authors.
Funding
Abstract
backgroundDespite the profound number of malignant pleural mesothelioma (MPM) patients now treated with programmed cell death 1 (PD-1) blockade, insight into the underpinnings of rational therapeutic strategies to treat resistance to checkpoint immunotherapy remains unrealized. Our objective was to develop a novel therapeutic approach to overcome primary resistance to PD-1 blockade in MPM.
methodsWe generated a transcriptome signature of resistance to PD-1 blockade in MPM patients treated with nivolumab (4 responders and 4 nonresponders). We used The Cancer Genome Atlas MPM cohort (n = 73) to determine what genomic alterations were associated with the resistance signature. We tested whether regulation of identified molecules could overcome resistance to PD-1 blockade in an immunocompetent mouse malignant mesothelioma model.
resultsImmunogenomic analysis by applying our anti-PD-1 resistance signature to The Cancer Genome Atlas cohort revealed that deletion of cyclin dependent kinase inhibitor 2A (CDKN2A) was highly associated with primary resistance to PD-1 blockade. Under the hypothesis that resistance to PD-1 blockade can be overcome by cyclin dependent kinase 4/6 (CDK4/6) inhibition, we tested whether CDK4/6 inhibitors could overcome resistance to PD-1 blockade in subcutaneous tumors derived from Cdkn2a
conclusionsWe identified a therapeutic target, CDK4/6, to overcome primary resistance to PD-1 blockade through comprehensive immunogenomic approaches. These data provide a rationale for undertaking clinical trials of CDK4/6 inhibitors in more than 40% of patients with MPM who demonstrate loss of CDKN2A.
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