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Pyrimidine addiction: An Achilles' heel of NF2-altered mesothelioma.
EMBO Mol. Med. 17, 2165-2167 (2025)
Therapeutic options for patients with mesothelioma remain scarce and five-year survival is a meager ten percent. According to data from three large studies, 36% of mesotheliomas harbor neurofibromatosis 2 (NF2) mutations or loss (https://bit.ly/4nGcRXk; accessed on 06.30.2025), yet no targeted therapy exists for this molecular subtype of the disease. In the current issue of EMBO Molecular Medicine, Xu et al, demonstrate that NF2-deficiency of mesothelioma cells releases an NF2-mediated Hippo-pathway restraint, activates the Yes-associated protein (YAP)–carbamoyl-phosphate synthetase 2, aspartate transcarbamylase, and dihydroorotase (CAD)/dihydroorotate dehydrogenase (DHODH) axis, and drives addiction to high-flux de novo pyrimidine biosynthesis (Xu et al, 2025). Moreover, the authors elegantly show that DHODH inhibitors elicit robust antitumor activity against NF2-altered mesothelioma and exhibit strong synergy with cisplatin, opening a new translational avenue for this tumor subtype.
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Publication type
Article: Journal article
Document type
Comment, Opinion
ISSN (print) / ISBN
1757-4676
e-ISSN
1757-4684
Journal
EMBO Molecular Medicine
Quellenangaben
Volume: 17,
Issue: 9,
Pages: 2165-2167
Publisher
Wiley
Publishing Place
Chichester
Reviewing status
Peer reviewed
Institute(s)
Institute of Lung Health and Immunity (LHI)