Cancer discovery
October 19, 2026 · via Europe PMC
H3K4me1-Mediated Epigenomic Priming of Chemoresistant Tumor States in Ovarian Cancer.
Landais Y, Bertorello J, Puerto MP, +18 more, Vallot C.
AI summary — for doctors, generated from the abstract only
In ovarian cancer, chemoresistant tumor states appear epigenetically primed by H3K4me1 before chemotherapy, and baseline composition relates to survival.
What was studied
Multimodal single-nucleus profiling of transcriptional programs and histone modifications from longitudinal frozen biopsies of 16 patients with high-grade serous ovarian cancer.
Key findings
- Proliferative and IFN-responsive states were depleted under chemotherapy while TNFα-associated and EMT-associated programs persisted or expanded
- These resistant programs were enriched for H3K4me1 before treatment
- Baseline tumor composition was associated with survival, and fibroblast remodeling accompanied malignant adaptation
Clinical relevance
Suggests resistance could be anticipated from pre-treatment biopsies, a step toward adaptive treatment strategies in HGSOC.
Who should care
Limitations
Very small cohort of 16 patients from a research setting, so findings are hypothesis-generating.
No change in practice; this supports future biomarker-guided strategies using pre-treatment biopsies.
This is an AI-generated summary of the published abstract, not a clinical recommendation. It may not reflect the full text or subsequent updates — verify against the original source before acting on it.
Abstract
Non-genetic intratumor heterogeneity underlies therapeutic failure in cancer, yet how resistant tumor states are encoded in patients remains unclear. In this study, we show that chemoresistant evolution in high-grade serous ovarian cancer (HGSOC) is prefigured by epigenetically primed tumor cell states present before therapy. Using multimodal single-nucleus approaches, we profile transcriptional programs and histone modifications from longitudinal frozen biopsies of 16 patients with HGSOC. Tumors comprise a limited set of functional states that evolve reproducibly under chemotherapy: proliferative and IFN-responsive states are depleted, whereas TNFα-associated and epithelial-mesenchymal transition-associated programs persist or expand. Chromatin profiling reveals that these resistant programs are broadly enriched for histone H3 lysine 4 monomethylation (H3K4me1) prior to treatment, indicating that features of resistance are epigenomically primed. Baseline tumor composition is associated with survival, and fibroblast remodeling accompanies malignant adaptation. Together, these findings identify epigenomic priming as a feature of chemoresistant tumor cell states and provide a scalable framework for anticipating resistance from biopsies.
Significance
Using a clinically compatible multimodal single-nucleus approach, the authors show that chemoresistant evolution in HGSOC is prefigured by epigenetically primed tumor cell states present before therapy.
DOI
10.1158/2159-8290.cd-26-0180
PMID
42895184
Research metadata (titles, abstracts, authors, publication dates) is sourced from Europe PMC, which aggregates content from PubMed/MEDLINE, PubMed Central, and other providers under the U.S. National Library of Medicine (NLM/NCBI). NLM does not claim copyright on abstracts; the original journal publishers or authors may hold rights to the full articles. AI-generated summaries are derived only from the abstract, never the full text, and are always labeled as AI-generated.
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