Congratulations to Dr Colm Ryan from UCD School of Medicine, the Conway Institute, and the School of Computer Science, as well as to Dr Francesco Raimondi and PhD student Anjan Venkatesh — also from the Conway Institute and School of Computer Science — and their collaborators, on a recent study which has found a new target with therapeutic potential for metastatic eye melanoma. The study, titled ‘The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types’, was led by Dr David Adams' group at the Wellcome Sanger Institute (UK), and was published in Nature Genetics on 4 July. Researchers used the gene-editing tool CRISPR to identify a pair of genes, CDS1 and CDS2, and found that the interaction between the two could serve as an effective therapeutic target for uveal melanoma, a rare form of eye cancer. The findings have implications for a range of other cancers and could potentially lead the way to the development of more targeted and effective cancer treatments.
Congratulations to everyone involved.
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.
Link to the journal article.
Link to the Wellcome Sanger Institute article.