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

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

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

Volume / Issue Vol. 1, Issue 1
Published July 13, 2026
ISSN 2041-1723
Publisher Nature Portfolio

Journal Info

Nature Communications

Nature Portfolio

ISSN: 2041-1723 Open Access Life Sciences

Authors (138)

R

Rebekka Wegmann

M

Michael Prummer

I

Ilaria Alborelli

R

Ruben Casanova

J

Jon Brugger

M

Magdalena M. Brune

B

Byron Calgua

S

Stefanie Engler

P

Pedro F. Ferreira

P

Paola Malsot

J

Julien Mena

S

Sujana Sivapatham

B

Bettina A. Sobottka-Brillout

T

Tibor A. Zwimpfer

M

Melike Ak

F

Faisal S. Al-Quaddoomi

S

Silvana I. Albert

J

Jonas Albinus

S

Sonali Andani

P

Per-Olof Attinger

M

Monica-Andreea Baciu-Drăgan

D

Daniel Baumhoer

B

Beatrice Beck-Schimmer

L

Lara Bernasconi

A

Anne Bertolini

X

Ximena Bonilla

L

Lars Bosshard

S

Stéphane Chevrier

N

Natalia Chicherova

R

Ricardo Coelho

M

Maya D’Costa

E

Esther Danenberg

N

Natalie R. Davidson

R

Reinhard Dummer

M

Martin Erkens

K

Katja Eschbach

C

Cinzia Esposito

A

André Fedier

J

Joanna Ficek-Pascual

A

Anja L. Frei

B

Bruno Frey

S

Sandra Goetze

L

Linda Grob

G

Gabriele Gut

D

Detlef Günther

P

Pirmin Haeuptle

S

Sylvia Herter

R

René Holtackers

T

Tamara Huesser

A

Alexander Immer

A

Anja Irmisch

F

Francis Jacob

A

Andrea Jacobs

T

Tim M. Jaeger

K

Katharina Jahn

A

Alva R. James

P

Philip M. Jermann

A

André Kahles

A

Abdullah Kahraman

Paul Scherrer Institute

W

Werner Kuebler

J

Jack Kuipers

C

Christian P. Kunze

C

Christian Kurzeder

M

Mitchell Levesque

U

Ulrike Lischetti

F

Flavio C. Lombardo

S

Sebastian Lugert

G

Gerd Maass

P

Philipp Markolin

M

Martin Mehnert

J

Julian M. Metzler

N

Nicola Miglino

E

Emanuela S. Milani

R

Riccardo Murri

C

Charlotte KY Ng

S

Stefan Nicolet

M

Marta Nowak

M

Monica Nunez Lopéz

P

Patrick GA Pedrioli

S

Salvatore Piscuoglio

L

Laurie Prélot

N

Natalie Rimmer

M

Mathilde Ritter

C

Christian Rommel

M

María L. Rosano-González

N

Natascha Santacroce

J

Jacobo Sarabia del Castillo

R

Ramona Schlenker

P

Petra C. Schwalie

S

Severin Schwan

T

Tobias Schär

G

Gabriela Senti

W

Wenguang Shao

B

Bettina Sobottka

V

Vipin T. Sreedharan

S

Stefan Stark

D

Daniel J. Stekhoven

T

Tanmay Tanna

A

Alexandre PA Theocharides

T

Tinu M. Thomas

V

Vinko Tosevski

N

Nora C. Toussaint

M

Mustafa A. Tuncel

M

Marina Tusup

A

Audrey Van Drogen

M

Marcus Vetter

T

Tatjana Vlajnic

S

Sandra Weber

W

Walter P. Weber

M

Michael Weller

F

Fabian Wendt

N

Norbert Wey

M

Mattheus HE Wildschut

S

Shuqing Yu

J

Johanna Ziegler

M

Marc Zimmermann

M

Martin Zoche

G

Gregor Zuend

R

Rudolf Aebersold

M

Marina Bacac

N

Niko Beerenwinkel

C

Christian Beisel

B

Bernd Bodenmiller

V

Viktor H. Koelzer

K

Kjong-Van Lehmann

M

Mitchell P. Levesque

H

Holger Moch

S

Simone Muenst

L

Lucas Pelkmans

M

Markus G. Manz

G

Gunnar Rätsch

F

Franziska Singer

B

Berend Snijder

A

Alexandre P. A. Theocharides

M

Markus Tolnay

A

Andreas Wicki

B

Bernd Wollscheid

V

Viola Heinzelmann-Schwarz