ArticleNature communications2025
Integrated molecular and clinical characterization of pulmonary large cell neuroendocrine carcinoma.
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Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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12citing papers in PubMed
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Who cites it
12 citing papers in PubMed.
- Brief Report: Proposed Clinical Trial Guidelines Based on Clinicopathologic Heterogeneity of Metastatic Pulmonary Large Cell Neuroendocrine Carcinoma.Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer · 2026Article
- De Novo Actionable Genomic Alterations in High-Grade Pulmonary Neuroendocrine Carcinomas: Therapeutic Implications of Targeted Treatment.Medical sciences (Basel, Switzerland) · 2026Article
- Proteogenomic characterization of pulmonary large-cell neuroendocrine carcinoma identifies molecular features and therapeutic strategy.Science advances · 2026Article
- Cancer Heterogeneity and Cancer Cell Plasticity: Molecular Mechanisms and Precision Therapy.MedComm · 2026Review
- Patients With Stage III PLCNEC Advocated for Radiotherapy Combined With Chemotherapy While With Stage IV Focus on Individualized Management: Evidence From SEER.Cancer reports (Hoboken, N.J.) · 2026Article
- Preoperative Lactate Dehydrogenase-to-Albumin Ratio as a Tumor-Host Biomarker of Early Recurrence and Survival in Resected Pulmonary Neuroendocrine Carcinomas: A Multicenter Observational Cohort Study.Medicina (Kaunas, Lithuania) · 2026Observational
- Targeting TPX2-dependent lineage plasticity by CDK4/6 inhibition reverses therapy resistance in neuroendocrine bladder carcinoma.Cell reports. Medicine · 2026Article
- Case report: ALK inhibitor-induced transformation of ALK fusion-positive lung adenocarcinoma to large cell neuroendocrine carcinoma.NPJ precision oncology · 2026Article
- Case Report: Marked elevation of serum procalcitonin before radiographic confirmation of recurrence in stage IVB pulmonary large cell neuroendocrine carcinoma.Frontiers in medicine · 2026Article
- Clinical utility of molecular profiling in rare lung neuroendocrine neoplasms.Frontiers in oncology · 2026Review
- Examining the effectiveness of follow-up chemotherapy in large cell neuroendocrine carcinoma: special emphasis on stage T1-2N0M0 according to 9Translational cancer research · 2025Article
- Non-functional, non-mutated multifocal neuroendocrine neoplasms in a postpartum female: a Case Report of an infrequent disease.Frontiers in medicine · 2025Article
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Authors and funding
74 authors.
Amin H Nassar *Department of Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8084-9105
Chul Kim *Division of Hematology and Oncology, Georgetown Cancer Institute, Washington, DC, USA.
Tolulope AdeyeluCaris Life Sciences, Phoenix, AZ, USA.
Elias Bou FarhatDivision of Pulmonary Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0009-0001-0063-0518
Hassan AbushukairDivision of Medical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Mehrdad RakaeeDivision of Pulmonary Medicine, Brigham and Women's Hospital, Boston, MA, USA.ORCID http://orcid.org/0000-0002-9080-0153
Kelsey MattesonDepartment of Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA.
Shun-Fat LauDepartment of Immunobiology, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0002-8527-3205
Yamato TakabeDepartment of Immunobiology, Yale University, New Haven, CT, USA.
Antonio OcejoDivision of Medical Oncology, Jackson Memorial Hospital, Miami, FL, USA.ORCID http://orcid.org/0000-0002-0664-2376
Fatemeh Ardeshir-LarijaniDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Ticiana LealDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Suresh RamalingamDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.ORCID http://orcid.org/0000-0002-0757-3106
Sumaiya AlamDepartment of Hematology and Medical Oncology, Winship Cancer Institute of Emory University, Atlanta, GA, USA.
Jhanelle E GrayDivision of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA.ORCID http://orcid.org/0000-0003-1304-7062
James HicksDivision of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA.
David KaldasDivision of Thoracic Oncology, Moffitt Cancer Center, Tampa, FL, USA.
Javier BaenaDepartment of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
Maria Zurera BerjagaDepartment of Medical Oncology, Hospital 12 de Octubre, Madrid, Spain.
Frank Aboubakar NanaDivision of Pneumology, Cliniques Universitaires Saint Luc, Bruxelles, Belgium.
Christian GroheKlinik für Pneumologie-Evangelische Lungenklinik, Berlin Buch, Berlin, Germany.
Heike LeudersKlinik für Pneumologie-Evangelische Lungenklinik, Berlin Buch, Berlin, Germany.
Fabrizio CitarellaDepartment of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.ORCID http://orcid.org/0000-0003-3096-4452
Alessio CortelliniDepartment of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.ORCID http://orcid.org/0000-0002-1209-5735
Emanuele Claudio MingoDepartment of Medicine and Surgery, Università Campus Bio-Medico di Roma, Rome, Italy.ORCID http://orcid.org/0009-0009-2918-7693
Danny PancirerDepartment of Medicine, Stanford Cancer Institute, Stanford, CA, USA.
Millie DasDepartment of Medicine, Stanford Cancer Institute, Stanford, CA, USA.
Timothy John Ellis-CaleoDepartment of Medicine, Stanford Cancer Institute, Stanford, CA, USA.ORCID http://orcid.org/0000-0002-3217-8335
Justin M CheungDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Jessica J LinDepartment of Medicine, Massachusetts General Hospital, Boston, MA, USA.
Alexander S WatsonDivision of Medical Oncology, University of Colorado Cancer Center, Denver, CO, USA.
D Ross CamidgeDivision of Medical Oncology, University of Colorado Cancer Center, Denver, CO, USA.
Arthi SridharDivision of Medical Oncology, Mayo Clinic, Rochester, MN, USA.ORCID http://orcid.org/0000-0002-8139-3322
Kaushal ParikhDivision of Medical Oncology, Mayo Clinic, Rochester, MN, USA.
Fionnuala CrowleyTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-9101-3912
Thomas U MarronTisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY, USA.ORCID http://orcid.org/0000-0001-5903-8191
Vanya AggarwalDivision of Hematology and Oncology, Georgetown Cancer Institute, Washington, DC, USA.
Murtaza AhmedDivision of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Kamya SankarDivision of Medical Oncology, Samuel Oschin Comprehensive Cancer Institute, Cedars Sinai Medical Center, Los Angeles, CA, USA.
Hassan KawtharanyDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.
Jun ZhangDivision of Medical Oncology, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, KS, USA.ORCID http://orcid.org/0000-0001-7886-6187
Dwight H OwenDivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Mingjia LiDivision of Medical Oncology, The Ohio State University Comprehensive Cancer Center, Columbus, OH, USA.
Misako NagasakaDepartment of Medicine, UC Irvine, Irvine, CA, USA.
David J PinatoDepartment of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK.ORCID http://orcid.org/0000-0002-3529-0103
Nichola AwosikaDepartment of Surgery & Cancer, Imperial College London, Hammersmith Hospital, London, UK.
Khaled AlhamadDivision of Medical Oncology, Huntsman Cancer Institute, Salt Lake City, UT, USA.
Sonam PuriDivision of Medical Oncology, Huntsman Cancer Institute, Salt Lake City, UT, USA.
Unaiza ZamanDivision of Medical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Divya M GuptaDivision of Medical Oncology, Northwestern University, Chicago, IL, USA.
Chelsea LauDivision of Medical Oncology, Northwestern University, Chicago, IL, USA.
Hina KhanDivision of Hematology and Oncology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Justin LiauwDivision of Hematology and Oncology, The Warren Alpert Medical School of Brown University, Providence, RI, USA.
Ana I VelazquezDivision of Medical Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.ORCID http://orcid.org/0000-0002-6153-5557
Tyiesha BrownDivision of Medical Oncology, University of California San Francisco Helen Diller Family Comprehensive Cancer Center, San Francisco, CA, USA.
Laura MolinerDivision of Medical Oncology, Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID http://orcid.org/0000-0002-1532-242X
Miguel MosteiroDivision of Medical Oncology, Institut Catala d'Oncologia, L'Hospitalet de Llobregat, Barcelona, Spain.ORCID http://orcid.org/0000-0002-3865-3184
Pedro RochaMedical Oncology Department, Vall d'Hebron University Hospital, Barcelona, Spain.
Mark EvansCaris Life Sciences, Phoenix, AZ, USA.
Ari VanderwaldeCaris Life Sciences, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0002-6842-2563
Andrew ElliottCaris Life Sciences, Phoenix, AZ, USA.ORCID http://orcid.org/0000-0001-8494-8031
Jorge NievaDivision of Medical Oncology, Norris Cancer Center, University of Southern California, Los Angeles, CA, USA.ORCID http://orcid.org/0000-0003-1605-4719
Gilberto LopesDivision of Medical Oncology, Jackson Memorial Hospital, Miami, FL, USA.
Patrick C MaPenn State Cancer Institute, Penn State Health Milton S. Hershey Medical Center, Penn State College of Medicine, Penn State University, Hershey, PA, USA.
Hossein BorghaeiDepartment of Hematology and Oncology, Fox Chase Cancer Center, Philadelphia, PA, USA.ORCID http://orcid.org/0000-0002-2577-4454
Matthew LeeDepartment of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, USA.
Lauren YoungDepartment of Oncology, Montefiore Medical Center/Albert Einstein College of Medicine, New York, NY, USA.
Raid AljumailyDivision of Medical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Haris MirzaDepartment of Pathology, Yale School of Medicine, New Haven, CT, USA.
David J KwiatkowskiDivision of Pulmonary Medicine, Brigham and Women's Hospital, Boston, MA, USA.
Roy S HerbstDepartment of Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-2535-5847
Richard A FlavellDepartment of Immunobiology, Yale University, New Haven, CT, USA.ORCID http://orcid.org/0000-0003-4461-0778
Abdul Rafeh NaqashDivision of Medical Oncology, Stephenson Cancer Center, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA. abdulrafeh-naqash@ou.edu.
Anne C ChiangDepartment of Medicine (Medical Oncology), Yale School of Medicine and Yale Cancer Center, New Haven, CT, USA. anne.chiang@yale.edu.ORCID http://orcid.org/0000-0002-2111-4694
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pulmonary large cell neuroendocrine carcinoma (LCNEC) is a rare, aggressive lung tumor marked by significant molecular heterogeneity. In a study of 590 patients across two independent cohorts, we observe comparable overall survival across treatment regimens (chemotherapy, chemoimmunotherapy, immunotherapy) without unexpected adverse events. Genomic analysis identifies distinct non-small cell lung cancer-like (NSCLC-like, KEAP1, KRAS, STK11 mutations) and SCLC-like (RB1, TP53 mutations) LCNEC subtypes, with 80% aligning with SCLC transcriptional profiles. Serial sampling reveals stable mutational but shifting transcriptomic landscapes over time. Here we show, elevated FGL-1 (a LAG-3 ligand) and SPINK1 expression in NSCLC-like LCNECs, and higher levels of DLL3 in SCLC-like LCNECs. Immunofluorescence confirms FGL-1 expression in NSCLC-like LCNECs, and H&E slide analyses indicates fewer tumor-infiltrating lymphocytes in LCNECs versus other lung cancers. These findings highlight LCNEC's distinct immunogenomic profile, supporting future investigations into LAG-3, SPINK1, and DLL3-targeted therapies.
Indexed as
Carcinoma, Large CellCarcinoma, NeuroendocrineLung NeoplasmsAgedBiomarkers, TumorCarcinoma, Non-Small-Cell LungFemaleGene Expression Regulation, NeoplasticHumansIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1Lymphocytes, Tumor-InfiltratingMaleMembrane ProteinsMiddle AgedMutationBiomarkers, TumorDLL3 protein, humanIntracellular Signaling Peptides and ProteinsKelch-Like ECH-Associated Protein 1Membrane ProteinsSPINK1 protein, humanTrypsin Inhibitor, Kazal Pancreatic
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