ArticleScientific reports2021
CDKN2A loss-of-function predicts immunotherapy resistance in non-small cell lung cancer.
Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers, 1 of them a synthesis that pooled it.
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Who cites it
73 citing papers in PubMed, 1 synthesis or guideline pooled it, 102 citations in OpenAlex.
- Identification of 4 autophagy-related genetic variants as risk factors for chronic lymphocytic leukemia.Blood advances · 2025Pooled it
- Targeting non-small cell lung cancer: Molecular mechanisms and clinical studies (Review).Oncology letters · 2026Review
- Tumor suppressor genotype influences the extent and mode of immunosurveillance in lung cancer.Nature communications · 2026Article
- Genomic Characterization of Lung Cancer in Never-Smokers Using Deep Learning.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2026Article
- Role of Spatial Heterogeneity in Muscle-Invasive Bladder Cancer on Overall Survival and Immunotherapy Response.Cancers · 2026Article
- Potential Immune Microenvironment Biomarkers in SCLC: J-TAIL-2 Observational Study.JTO clinical and research reports · 2026Article
- Prevalence and Actionability of MTAP Loss in Oncogene-Driven Lung Cancer.bioRxiv : the preprint server for biology · 2026Article
- Evaluation of quantitative polymerase chain reaction for detecting BRCA1 or BRCA2 copy number loss in high-grade serous ovarian cancer.Scientific reports · 2026Article
- Primary Pulmonary NUT Carcinoma: A Case Illustration of Therapeutic Challenges and Review of Emerging Targeted Therapies.Case reports in oncological medicine · 2026Article
- Loss ofJournal of Cancer · 2026Article
- CDK4/6 inhibition with dual immunotherapy in chemorefractory SMARCA4-deficient undifferentiated tumor: a case report.Frontiers in immunology · 2026Article
- Molecular and immune determinants of response in locally advanced deficient DNA mismatch repair/microsatellite instability-high gastric or gastroesophageal junction adenocarcinoma treated with neoadjuvant chemoimmunotherapy.Cell communication and signaling : CCS · 2025Article
- CDKN2A deletion is associated with immune desertification in diffuse pleural mesothelioma.Journal of experimental & clinical cancer research : CR · 2025Article
- Allelic expression imbalance of CDKN2A variants in childhood acute lymphoblastic leukemia.Cellular oncology (Dordrecht, Netherlands) · 2025Article
- A Pilot Study: Contrasting Genomic Profiles of Lung Adenocarcinoma Between Patients of European and Latin American Ancestry.International journal of molecular sciences · 2025Article
- Comprehensive analysis of prognosis and tumor immune microenvironment of cuproptosis-related gene CDKN2A in lung adenocarcinoma.BMC pulmonary medicine · 2025Article
- Harnessing Plasma Biomarkers to Predict Immunotherapy Outcomes in Hepatocellular Carcinoma: The Role of cfDNA, ctDNA, and Cytokines.International journal of molecular sciences · 2025Article
- DNA Methylation in Lung Cancer: Predictive Biomarkers for Effective Immunotherapy.International journal of general medicine · 2025Review
- Diabetes-associated differentially expressed genes as prognostic biomarkers and therapeutic targets in endometrial cancer: a comprehensive molecular analysis.Frontiers in oncology · 2025Article
- Updating the genomic and clinicopathologic features of thoracic SMARCA4-deficient undifferentiated tumor: a mini-series including a long-term survivor.Frontiers in oncology · 2025Article
13 more citing papers are in PubMed but not listed here.
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21 authors at 2 institutions in 1 country.
Funding
Abstract
Immune checkpoint blockade (ICB) improves outcomes in non-small cell lung cancer (NSCLC) though most patients progress. There are limited data regarding molecular predictors of progression. In particular, there is controversy regarding the role of CDKN2A loss-of-function (LOF) in ICB resistance. We analyzed 139 consecutive patients with advanced NSCLC who underwent NGS prior to ICB initiation to explore the association of CDKN2A LOF with clinical outcomes. 73% were PD-L1 positive (≥ 1%). 48% exhibited high TMB (≥ 10 mutations/megabase). CDKN2A LOF was present in 26% of patients and was associated with inferior PFS (multivariate hazard ratio [MVA-HR] 1.66, 95% CI 1.02-2.63, p = 0.041) and OS (MVA-HR 2.08, 95% CI 1.21-3.49, p = 0.0087) when compared to wild-type (WT) patients. These findings held in patients with high TMB (median OS, LOF vs. WT 10.5 vs. 22.3 months; p = 0.069) and PD-L1 ≥ 50% (median OS, LOF vs. WT 11.1 vs. 24.2 months; p = 0.020), as well as in an independent dataset. CDKN2A LOF vs. WT tumors were twice as likely to experience disease progression following ICB (46% vs. 21%; p = 0.021). CDKN2A LOF negatively impacts clinical outcomes in advanced NSCLC treated with ICB, even in high PD-L1 and high TMB tumors. This novel finding should be prospectively validated and presents a potential therapeutic target.
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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.