ArticleCancer discovery2021
Multiomic Analysis of Lung Tumors Defines Pathways Activated in Neuroendocrine Transformation.
Article in Cancer discovery, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 2 of them syntheses that pooled it.
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The trial behind it
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Who cites it
121 citing papers in PubMed, 2 syntheses or guidelines pooled it, 170 citations in OpenAlex.
- Histological transformation in lung cancer: a single-arm meta-analysis and systematic review.BMC cancer · 2026Pooled it
- [Histological Transformation from Non-small Cell Lung Cancer to Small Cell Lung Cancer Induced by Immune Checkpoint Inhibitor Therapy: A Case Report and Literature Review].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2025Pooled it
- Genes, fuel, and fate in lung cancer.Biochemical Society transactions · 2026Review
- PIK3CA in the transformation of EGFR ‑mutant lung adenocarcinoma to small cell lung cancer following acquired targeted therapy resistance.Chinese medical journal · 2026Article
- PAX5 modulates vascularization and contributes to neuroendocrine lineage transition during carcinoma progression.The Journal of clinical investigation · 2026Article
- Article
- Epigenetics in lung cancer precision medicine: from bench to bedside-a narrative review.Translational lung cancer research · 2026Review
- Nicotinic Acid Restriction Enhances the Therapeutic Benefit of NAMPT Inhibition in Small-Cell Lung Cancer Models.Cancer science · 2026Article
- [Expert Consensus on Immunotherapy for Extensive-stage Small Cell Lung Cancer Based on Molecular Subtyping].Zhongguo fei ai za zhi = Chinese journal of lung cancer · 2026Review
- Review
- Squamous-state excursions activate APOBEC3A in cancer.bioRxiv : the preprint server for biology · 2026Article
- Characterization of natural killer (NK) cells in lung adenocarcinoma and construction of an NK risk signature based on single-cell and macromolecular RNA-seg data.Discover oncology · 2026Article
- Distinct mutation landscape with similar immune microenvironment in primary simultaneous operable squamous cell carcinoma and peripheral-type small-cell lung cancer.Translational lung cancer research · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Mutational Landscape and Treatment Response in Extensive-Stage Small-Cell Lung Cancer: A Single-Center Real-World Analysis.Current oncology (Toronto, Ont.) · 2026Article
- Spatial multi-omics unveils the monoclonal origin, neuroendocrine plasticity, and microenvironment niches in combined small-cell lung cancer.Cell reports. Medicine · 2026Article
- Stem cell control and cancer initiation by an autocrine, injury-activated Igf complex.bioRxiv : the preprint server for biology · 2026Article
- Pleomorphic Carcinoma With EGFR and Concomitant Mutations Transformed From Lung Adenocarcinoma: A Case Report.Cancer reports (Hoboken, N.J.) · 2026Article
- Tolerance and Resistance to Targeted Therapy in NSCLC: Emerging Concepts and Strategies.JTO clinical and research reports · 2026Review
- Deciphering double-negative prostate cancer: from aggressive subtype to novel therapeutic paradigms.Cell communication and signaling : CCS · 2026Review
61 more citing papers are in PubMed but not listed here.
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36 authors at 2 institutions in 1 country.
Funding
Abstract
Lineage plasticity is implicated in treatment resistance in multiple cancers. In lung adenocarcinomas (LUAD) amenable to targeted therapy, transformation to small cell lung cancer (SCLC) is a recognized resistance mechanism. Defining molecular mechanisms of neuroendocrine (NE) transformation in lung cancer has been limited by a paucity of pre/posttransformation clinical samples. Detailed genomic, epigenomic, transcriptomic, and protein characterization of combined LUAD/SCLC tumors, as well as pre/posttransformation samples, supports that NE transformation is primarily driven by transcriptional reprogramming rather than mutational events. We identify genomic contexts in which NE transformation is favored, including frequent loss of the 3p chromosome arm. We observed enhanced expression of genes involved in the PRC2 complex and PI3K/AKT and NOTCH pathways. Pharmacologic inhibition of the PI3K/AKT pathway delayed tumor growth and NE transformation in an EGFR-mutant patient-derived xenograft model. Our findings define a novel landscape of potential drivers and therapeutic vulnerabilities of NE transformation in lung cancer. SIGNIFICANCE: The difficulty in collection of transformation samples has precluded the performance of molecular analyses, and thus little is known about the lineage plasticity mechanisms leading to LUAD-to-SCLC transformation. Here, we describe biological pathways dysregulated upon transformation and identify potential predictors and potential therapeutic vulnerabilities of NE transformation in the lung. See related commentary by Meador and Lovly, p. 2962. This article is highlighted in the In This Issue feature, p. 2945.
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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.