Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers

Autor: Van Nyen, Tom, Planque, Mélanie, van Wagensveld, Lilian, Duarte, Joao A.G., Zaal, Esther A., Talebi, Ali, Rossi, Matteo, Körner, Pierre René, Rizzotto, Lara, Moens, Stijn, De Wispelaere, Wout, Baiden-Amissah, Regina E.M., Sonke, Gabe S., Horlings, Hugo M., Eelen, Guy, Berardi, Emanuele, Swinnen, Johannes V., Berkers, Celia R., Carmeliet, Peter, Lambrechts, Diether, Davidson, Ben, Agami, Reuven, Fendt, Sarah Maria, Annibali, Daniela, Amant, Frédéric, Veterinaire biochemie, Faculteit Diergeneeskunde, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics
Přispěvatelé: Obstetrics and Gynaecology, CCA - Cancer biology and immunology, ARD - Amsterdam Reproduction and Development, Obstetrie & Gynaecologie, RS: GROW - R2 - Basic and Translational Cancer Biology, Veterinaire biochemie, Faculteit Diergeneeskunde, Sub Biomol.Mass Spectrometry & Proteom., Biomolecular Mass Spectrometry and Proteomics, Molecular Genetics
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Serine/pharmacology
Chemistry(all)
Drug Resistance
General Physics and Astronomy
Carcinoma
Ovarian Epithelial
Poly(ADP-ribose) Polymerase Inhibitors
Physics and Astronomy(all)
Biochemistry
General Biochemistry
Genetics and Molecular Biology
Local/drug therapy
Platinum/pharmacology
SDG 3 - Good Health and Well-being
Serine
Humans
General
Platinum
Carcinoma
Ovarian Epithelial/drug therapy
Ovarian Neoplasms
Multidisciplinary
Biochemistry
Genetics and Molecular Biology(all)
Carcinoma
Ovarian Neoplasms/drug therapy
General Chemistry
Poly(ADP-ribose) Polymerase Inhibitors/pharmacology
Neoplasm Recurrence
Neoplasm Recurrence
Local/drug therapy
Ovarian Epithelial/drug therapy
Drug Resistance
Neoplasm
Neoplasm
Female
Poly(ADP-ribose) Polymerases/pharmacology
Neoplasm Recurrence
Local
Poly(ADP-ribose) Polymerases
Genetics and Molecular Biology(all)
Zdroj: Nature communications, 13(1):4578. Nature Publishing Group
Nature Communications, 13(1):4578. Nature Publishing Group
Van Nyen, T, Planque, M, van Wagensveld, L, Duarte, J A G, Zaal, E A, Talebi, A, Rossi, M, Körner, P R, Rizzotto, L, Moens, S, De Wispelaere, W, Baiden-Amissah, R E M, Sonke, G S, Horlings, H M, Eelen, G, Berardi, E, Swinnen, J V, Berkers, C R, Carmeliet, P, Lambrechts, D, Davidson, B, Agami, R, Fendt, S M, Annibali, D & Amant, F 2022, ' Serine metabolism remodeling after platinum-based chemotherapy identifies vulnerabilities in a subgroup of resistant ovarian cancers ', Nature Communications, vol. 13, no. 1, 4578 . https://doi.org/10.1038/s41467-022-32272-6
Nature Communications, 13(1), 1. Nature Publishing Group
Nature Communications
ISSN: 2041-1723
Popis: Resistance to platinum-based chemotherapy represents a major clinical challenge for many tumors, including epithelial ovarian cancer. Patients often experience several response-relapse events, until tumors become resistant and life expectancy drops to 12-15 months. Despite improved knowledge of the molecular determinants of platinum resistance, the lack of clinical applicability limits exploitation of many potential targets, leaving patients with limited options. Serine biosynthesis has been linked to cancer growth and poor prognosis in various cancer types, however its role in platinum-resistant ovarian cancer is not known. Here, we show that a subgroup of resistant tumors decreases phosphoglycerate dehydrogenase (PHGDH) expression at relapse after platinum-based chemotherapy. Mechanistically, we observe that this phenomenon is accompanied by a specific oxidized nicotinamide adenine dinucleotide (NAD+) regenerating phenotype, which helps tumor cells in sustaining Poly (ADP-ribose) polymerase (PARP) activity under platinum treatment. Our findings reveal metabolic vulnerabilities with clinical implications for a subset of platinum resistant ovarian cancers. ispartof: NATURE COMMUNICATIONS vol:13 issue:1 ispartof: location:England status: published
Databáze: OpenAIRE
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