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DOI 10.1038/s41467-026-74585-w

Медицинская библиотека · Nature communications · 2026

A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy.

Jacob Francis, Wegmann Rebekka, Ficek-Pascual Joanna, Lischetti Ulrike, Kuipers Jack, Chevrier Stéphane, Prummer Michael, Toussaint Nora C, Alborelli Ilaria, Coelho Ricardo, Casanova Ruben, Goetze Sandra, Gut Gabriele, Baciu-Drăgan Monica-Andreea, Bertolini Anne, Bonilla Ximena, Brugger Jon, Brune Magdalena M, Calgua Byron, Engler Stefanie, Esposito Cinzia, Ferreira Pedro F, Jacobs Andrea, Lombardo Flavio C, Malsot Paola, Mena Julien, Miglino Nicola, Milani Emanuela S, Sarabia Del Castillo Jacobo, Sivapatham Sujana, Sobottka-Brillout Bettina A, Tanna Tanmay, Zwimpfer Tibor A, TumorProfiler Consortium, Aebersold Rudolf, Bacac Marina, Beerenwinkel Niko, Beisel Christian, Bodenmiller Bernd, Koelzer Viktor H, Lehmann Kjong-Van, Levesque Mitchell P, Moch Holger, Muenst Simone, Pelkmans Lucas, Manz Markus G, Rätsch Gunnar, Singer Franziska, Snijder Berend, Theocharides Alexandre P A, Tolnay Markus, Wicki Andreas, Wollscheid Bernd, Heinzelmann-Schwarz Viola

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Аннотация

In women with high-grade serous ovarian cancer, chemotherapy remains the primary standard treatment, despite growing recognition of the disease as highly heterogeneous. Here, we examine the feasibility and clinical utility of comprehensive multimodal molecular profiling to inform treatment decisions. We analyze blood, single-cell and bulk tumor tissue, and malignant ascites using up to eleven technologies (DNA, RNA, protein, and functional assays) within a four-week turnaround time. Hypothetical treatment recommendations are altered for 76% of patients, and multi-omics-guided maintenance therapy is associated with prolonged overall survival in a subset of patients. Subsequent cohort analysis reveals distinct cellular and molecular profiles in ascites-derived single-cells compared to solid tumor tissue, unique per-patient ex vivo drug responses, and a marked increase in cancer cell heterogeneity following chemotherapy exposure. This coincides with genomic signature alterations in whole-genome-amplified patients. Our data suggest that molecularly guided treatments should be tested as adjuvant therapies prior to chemotherapy in the future.

Для цитирования: Jacob Francis, Wegmann Rebekka, Ficek-Pascual Joanna, Lischetti Ulrike, Kuipers Jack, Chevrier Stéphane, Prummer Michael, Toussaint Nora C, Alborelli Ilaria, Coelho Ricardo, Casanova Ruben, Goetze Sandra, Gut Gabriele, Baciu-Drăgan Monica-Andreea, Bertolini Anne, Bonilla Ximena, Brugger Jon, Brune Magdalena M, Calgua Byron, Engler Stefanie, Esposito Cinzia, Ferreira Pedro F, Jacobs Andrea, Lombardo Flavio C, Malsot Paola, Mena Julien, Miglino Nicola, Milani Emanuela S, Sarabia Del Castillo Jacobo, Sivapatham Sujana, Sobottka-Brillout Bettina A, Tanna Tanmay, Zwimpfer Tibor A, TumorProfiler Consortium, Aebersold Rudolf, Bacac Marina, Beerenwinkel Niko, Beisel Christian, Bodenmiller Bernd, Koelzer Viktor H, Lehmann Kjong-Van, Levesque Mitchell P, Moch Holger, Muenst Simone, Pelkmans Lucas, Manz Markus G, Rätsch Gunnar, Singer Franziska, Snijder Berend, Theocharides Alexandre P A, Tolnay Markus, Wicki Andreas, Wollscheid Bernd, Heinzelmann-Schwarz Viola. A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy.. Nature communications. 2026. DOI: 10.1038/s41467-026-74585-w.

Предметные рубрики MeSH

HumansFemaleOvarian NeoplasmsPrecision MedicineGene Expression ProfilingGene Expression Regulation, NeoplasticBiomarkers, TumorAntineoplastic AgentsAscites
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