Nature Communications (Aug 2022)
Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers
- Tom Van Nyen,
- Mélanie Planque,
- Lilian van Wagensveld,
- Joao A. G. Duarte,
- Esther A. Zaal,
- Ali Talebi,
- Matteo Rossi,
- Pierre-René Körner,
- Lara Rizzotto,
- Stijn Moens,
- Wout De Wispelaere,
- Regina E. M. Baiden-Amissah,
- Gabe S. Sonke,
- Hugo M. Horlings,
- Guy Eelen,
- Emanuele Berardi,
- Johannes V. Swinnen,
- Celia R. Berkers,
- Peter Carmeliet,
- Diether Lambrechts,
- Ben Davidson,
- Reuven Agami,
- Sarah-Maria Fendt,
- Daniela Annibali,
- Frédéric Amant
Affiliations
- Tom Van Nyen
- Gynecological Oncology Laboratory, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Mélanie Planque
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB
- Lilian van Wagensveld
- Department of Obstetrics and Gynecology, Maastricht University Medical Centre
- Joao A. G. Duarte
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB
- Esther A. Zaal
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University
- Ali Talebi
- Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Matteo Rossi
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB
- Pierre-René Körner
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Lara Rizzotto
- TRACE PDX Platform, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Stijn Moens
- Gynecological Oncology Laboratory, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Wout De Wispelaere
- Gynecological Oncology Laboratory, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Regina E. M. Baiden-Amissah
- Gynecological Oncology Laboratory, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Gabe S. Sonke
- Department of Medical Oncology, The Netherlands Cancer Institute
- Hugo M. Horlings
- Division of Molecular Pathology, The Netherlands Cancer Institute
- Guy Eelen
- Laboratory of Angiogenesis and Vascular Metabolism, VIB-KU Leuven Center for Cancer Biology, VIB, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Emanuele Berardi
- Department of Development and Regeneration, KU Leuven
- Johannes V. Swinnen
- Laboratory of Lipid Metabolism and Cancer, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Celia R. Berkers
- Biomolecular Mass Spectrometry and Proteomics, Bijvoet Center for Biomolecular Research, Utrecht University
- Peter Carmeliet
- Laboratory of Angiogenesis and Vascular Metabolism, VIB-KU Leuven Center for Cancer Biology, VIB, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Diether Lambrechts
- Laboratory for Translational Genetics, Department of Human Genetics, KU Leuven
- Ben Davidson
- University of Oslo, Faculty of Medicine, Institute of Clinical Medicine
- Reuven Agami
- Division of Oncogenomics, Oncode Institute, The Netherlands Cancer Institute
- Sarah-Maria Fendt
- Laboratory of Cellular Metabolism and Metabolic Regulation, VIB-KU Leuven Center for Cancer Biology, VIB
- Daniela Annibali
- Gynecological Oncology Laboratory, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- Frédéric Amant
- Gynecological Oncology Laboratory, Department of Oncology, KU Leuven and Leuven Cancer Institute (LKI)
- DOI
- https://doi.org/10.1038/s41467-022-32272-6
- Journal volume & issue
-
Vol. 13,
no. 1
pp. 1 – 19
Abstract
Metabolic reprogramming is associated with cancer development and therapy resistance. Here, the authors show that downregulation of the serine biosynthesis enzyme PHGDH in a fraction of patients is associated with relapse in platinum-treated ovarian cancers and to NAD+ and PARP activity upregulation.