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

Authors

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

Published in

Nature communications. Jul 13, 2026. Epub Jul 13, 2026.

Abstract

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.

PMID:
42443179
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.

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