ArticleThe Journal of clinical investigation2026
Plasma nucleosome profiling reports on tumor burden and molecular subtypes in small cell lung cancer.
Article in The Journal of clinical investigation, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 6 registered trials, which are not on this map. Not yet cited in PubMed.
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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.
Tissue Procurement and Natural History Study of Patients With Non-Small Cell Lung Cancer, Small Cell Lung Cancer, Extrapulmonary Small Cell Cancer, Pulmonary Neuroendocrine Tumors, and Thymic Epithelial Tumors
Phase I/II Study of the Anti-Programmed Death Ligand-1 Antibody Durvalumab (MEDI4736) in Combination With Olaparib and/or Cediranib for Advanced Solid Tumors and Advanced or Recurrent Ovarian, Triple Negative Breast, Lung, Prostate and Colorectal Cancers
A Phase I/II Trial of Topotecan With VX-970 (M6620), an ATR Kinase Inhibitor in Small Cell Cancers
A Phase I/II Trial of EP0057, a Nanoparticle Camptothecin With Olaparib in Patients With Relapsed/Refractory Small Cell Lung, Bladder and Prostate Cancers
Safety Run-In and Phase II Trial of M7824 and Topotecan or Temozolomide in Relapsed Small Cell Cancers
Randomized Phase II Trial of Topotecan Plus M6620 (VX-970, Berzosertib) Vs. Topotecan Alone in Patients With Relapsed Small-Cell Lung Cancer
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33 authors.
Funding
Abstract
BACKGROUNDSmall-cell lung cancer (SCLC) is an aggressive malignancy with a poor prognosis and marked transcriptional heterogeneity that may drive distinct therapeutic vulnerabilities. Clinical translation of molecular subtyping has been limited by restricted access to tumor biopsies, particularly at relapse.METHODSWe applied chromatin immunoprecipitation of cell-free nucleosomes carrying active histone modifications followed by sequencing (cfChIP-seq) to 441 plasma samples from individuals with advanced SCLC, other neuroendocrine carcinomas, or non-SCLC cancers, as well as from healthy controls. Plasma cfChIP-seq profiles were integrated with matched tumor transcriptomes from 73 samples, including 41 time-matched pairs.RESULTScfChIP-seq captured the epigenetic and transcriptional landscape of tumor-derived cell-free DNA (cfDNA), including SCLC tissue- and cell-of-origin signatures. A quantitative cfChIP-seq-derived SCLC score tracked radiographic tumor burden and was associated with prognosis. Signals at promoters of lineage-defining transcription factor genes, including ASCL1, NEUROD1, POU2F3, and ATOH1, correlated strongly with matched tumor RNA expression and supported noninvasive inference of SCLC transcriptional subtypes directly from plasma.CONCLUSIONPlasma cfChIP-seq provides a practical liquid biopsy platform for real-time assessment of tumor burden, tumor state, and molecular subtype in SCLC. These findings support further development of cfChIP-seq for precision monitoring and subtype-informed therapeutic stratification in SCLC.TRIAL REGISTRATIONClinicalTrials.gov NCT02484404, NCT02487095, NCT02769962, NCT03554473, NCT03896503, and NCT02146170.FUNDINGCenter for Cancer Research; Intramural Program of the NCI (ZIA BC 011793); European Research Council (ERC) (Adg no. 101019560 "cfChIP").
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