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Hung Trinh: CRISPR Screening Reveals New Drug Target for Aggressive Eye Cancer

Hung Trinh/LinkedIn

Jul 15, 2025, 16:38

Hung Trinh: CRISPR Screening Reveals New Drug Target for Aggressive Eye Cancer

Hung Trinh, Senior VP of Operations at Seneca Therapeutics, Inc., shared on LinkedIn about a recent paper shared by Pui Ying Chan et al. published in Nature:

“CRISPR screening reveals new drug target for aggressive eye cancer

In an article published in Nature Genetics, scientists from the Welcome Sanger Institute and their collaborators used CRISPR screening—a gene-editing tool – to reveal two genes, CDS1 and CDS2, which strongly rely on each other in metastatic eye melanoma. This could pave the way for more targeted and effective cancer treatments, which are currently lacking.

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.

Nature Genetics.”

Hung Trinh

Title: The synthetic lethal interaction between CDS1 and CDS2 is a vulnerability in uveal melanoma and across multiple tumor types

Authors: Pui Ying Chan, Diana Alexander, Ishan Mehta, Larissa Satiko Alcantara Sekimoto Matsuyama, Victoria Harle, Rebeca Olvera-León, Jun Sung Park, Fernanda G. Arriaga-González, Louise van der Weyden, Saamin Cheema, Vivek Iyer, Victoria Offord, David Barneda, Phillip T. Hawkins, Len Stephens, Zuza Kozik, Michael Woods, Kim Wong, Gabriel Balmus, Alessandro Vinceti, Nicola A. Thompson, Martin Del Castillo Velasco-Herrera, Lodewyk Wessels, Joris van de Haar, Emanuel Gonçalves, Sanju Sinha, Martha Estefania Vázquez-Cruz, Luisa Bisceglia, Francesco Raimondi, Jyoti Choudhary, Sumeet Patiyal, Anjan Venkatesh, Francesco Iorio, Colm J. Ryan and David J. Adams

Read the full article.

Hung Trinh

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Alessandro Vinceti Anjan Venkatesh cancer cancer treatment Colm J. Ryan CRISPR screening David Barneda David J. Adams Diana Alexander Emanuel Goncalves Fernanda G. Arriaga-González Francesco Iorio Francesco Raimondi Gabriel Balmus Hung Trinh Ishan Mehta Joris van de Haar Jun Sung Park Jyoti Choudhary Kim Wong Larissa Satiko Alcantara Sekimoto Matsuyama Len Stephens Lodewyk Wessels Louise van der Weyden Luisa Bisceglia Martha Estefania Vázquez-Cruz Martin Del Castillo Velasco-Herrera metastatic eye melanoma Michael Woods Nature Genetics Nicola A. Thompson OncoDaily Oncology Phillip T. Hawkins Pui Ying Chan Rebeca Olvera-León Saamin Cheema Sanju Sinha Sumeet Patiyal Victoria Harle Victoria Offord Vivek Iyer Zuza Kozik

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