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 |
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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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