ArticleNature genetics2025
The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types.
Article in Nature genetics, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed.
- Article
- Essentiality-driven prediction of anticancer drug responses in preclinical and clinical contexts.iScience · 2026Article
- GDF15 Reprograms the Microenvironment to Drive Liver Metastasis of Uveal Melanoma.Cancer research · 2026Article
- Identification of central regulators associated with serum triglyceride metabolism during growth and development in chickens.Poultry science · 2026Article
- Gene therapy for uveal melanoma.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Decoding protein-phospholipid interaction networks in cancer: the role of acyl-chain remodeling.RSC chemical biology · 2026Review
- Pancancer Fine-Mapping of Mutational Intolerance Identifies CHEK1 as an Immunosuppressive Driver in Lung Adenocarcinoma.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Ferroptosis as a therapeutic vulnerability in ARID1A-deficient bladder cancer.Communications biology · 2026Article
- Article
- Chromosome 3p deletion leads to extensive genomic alterations in diverse cancers and confers synthetic lethality in uveal melanoma.bioRxiv : the preprint server for biology · 2026Article
- Synthetic lethality in cancer therapy: Mechanisms, models and clinical translation for overcoming therapeutic resistance.Clinical and translational medicine · 2026Review
- Multi-omics comprehensive analysis identified KIF22 and KRAS as highly synthetic lethal pairs for triple-negative breast cancer.Frontiers in oncology · 2026Article
- Toward Precision Medicine: Gene Therapy Applications in the Management of Uveal Melanoma.Cancer reports (Hoboken, N.J.) · 2025Review
- A compendium of synthetic lethal gene pairs defined by extensive combinatorial pan-cancer CRISPR screening.Genome biology · 2025Article
- Cytidine diphosphate diacylglycerol synthase 2 is a synthetic lethal target in mesenchymal-like cancers.Nature genetics · 2025Article
Corrections and comments
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Authors and funding
35 authors.
Funding
Abstract
Metastatic uveal melanoma is an aggressive disease with limited effective therapeutic options. To comprehensively map monogenic and digenic dependencies, we performed CRISPR-Cas9 screening in ten extensively profiled human uveal melanoma cell line models. Analysis involved genome-wide single-gene and combinatorial paired-gene CRISPR libraries. Among our 76 uveal melanoma-specific essential genes and 105 synthetic lethal gene pairs, we identified and validated the CDP-diacylglycerol synthase 2 gene (CDS2) as a genetic dependency in the context of low CDP-diacylglycerol synthase 1 gene (CDS1) expression. We further demonstrate that CDS1/CDS2 forms a synthetic lethal interaction in vivo and reveal that CDS2 knockout results in the disruption of phosphoinositide synthesis and increased cellular apoptosis and that re-expression of CDS1 rescues this cell fitness defect. We extend our analysis using pan-cancer data, confirming increased CDS2 essentiality in diverse tumor types with low CDS1 expression. Thus, the CDS1/CDS2 axis is a therapeutic target across a range of cancers.
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