A tumor profiling resource for ovarian cancer: insights into chemotherapy-driven heterogeneity and personalized treatment strategy
Abstract
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.
Article Details
Authors (138)
Rebekka Wegmann
Michael Prummer
Ilaria Alborelli
Ruben Casanova
Jon Brugger
Magdalena M. Brune
Byron Calgua
Stefanie Engler
Pedro F. Ferreira
Paola Malsot
Julien Mena
Sujana Sivapatham
Bettina A. Sobottka-Brillout
Tibor A. Zwimpfer
Melike Ak
Faisal S. Al-Quaddoomi
Silvana I. Albert
Jonas Albinus
Sonali Andani
Per-Olof Attinger
Monica-Andreea Baciu-Drăgan
Daniel Baumhoer
Beatrice Beck-Schimmer
Lara Bernasconi
Anne Bertolini
Ximena Bonilla
Lars Bosshard
Stéphane Chevrier
Natalia Chicherova
Ricardo Coelho
Maya D’Costa
Esther Danenberg
Natalie R. Davidson
Reinhard Dummer
Martin Erkens
Katja Eschbach
Cinzia Esposito
André Fedier
Joanna Ficek-Pascual
Anja L. Frei
Bruno Frey
Sandra Goetze
Linda Grob
Gabriele Gut
Detlef Günther
Pirmin Haeuptle
Sylvia Herter
René Holtackers
Tamara Huesser
Alexander Immer
Anja Irmisch
Francis Jacob
Andrea Jacobs
Tim M. Jaeger
Katharina Jahn
Alva R. James
Philip M. Jermann
André Kahles
Abdullah Kahraman
Paul Scherrer Institute
Werner Kuebler
Jack Kuipers
Christian P. Kunze
Christian Kurzeder
Mitchell Levesque
Ulrike Lischetti
Flavio C. Lombardo
Sebastian Lugert
Gerd Maass
Philipp Markolin
Martin Mehnert
Julian M. Metzler
Nicola Miglino
Emanuela S. Milani
Riccardo Murri
Charlotte KY Ng
Stefan Nicolet
Marta Nowak
Monica Nunez Lopéz
Patrick GA Pedrioli
Salvatore Piscuoglio
Laurie Prélot
Natalie Rimmer
Mathilde Ritter
Christian Rommel
María L. Rosano-González
Natascha Santacroce
Jacobo Sarabia del Castillo
Ramona Schlenker
Petra C. Schwalie
Severin Schwan
Tobias Schär
Gabriela Senti
Wenguang Shao
Bettina Sobottka
Vipin T. Sreedharan
Stefan Stark
Daniel J. Stekhoven
Tanmay Tanna
Alexandre PA Theocharides
Tinu M. Thomas
Vinko Tosevski
Nora C. Toussaint
Mustafa A. Tuncel
Marina Tusup
Audrey Van Drogen
Marcus Vetter
Tatjana Vlajnic
Sandra Weber
Walter P. Weber
Michael Weller
Fabian Wendt
Norbert Wey
Mattheus HE Wildschut
Shuqing Yu
Johanna Ziegler
Marc Zimmermann
Martin Zoche
Gregor Zuend
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