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April 23, 2026Genes0 citationsOpen Access

Landscape of Gene Essentiality in Cancer Cell Death Pathways

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SLShangjia LiZZZhimo ZhuCYChen Yang

Key Points

  • This study aims to understand the contribution of gene essentiality in regulated cell death pathways to cancer therapy.
  • Analyzed 1150 cancer cell lines from the Dependency Map database.
  • Categorized genes based on essentialities in 12 cell death pathways.
  • Classified genes as always essential, partial essential, or rare essential.
  • Identified 23 genes as always essential, 47 as partial essential, and 549 as rare essential across the pathways.
  • Parthanatos and Pyroptosis pathways contained only rare essential genes.
  • Detailed classifications provided specific counts of essential genes for various cell death mechanisms.

Abstract

Background/Objectives: Regulated cell death (RCD), a process that relies on a series of molecular mechanisms, can be targeted to eliminate superfluous, irreversibly damaged, and potentially harmful cells. In this research, we want to better understand how the cell death pathway contributes to cancer therapy. Methods: We studied 1150 cancer cells in the Dependency Map (DepMap) database for 12 distinct cell death pathways and assessed their gene essentialities. Genes which are essential in 90% or more of cancer cell lines are called always essential, or partial essential if falling into (10%, 90%), or rare essential if they are essential in less than 10% of cancer cell lines. Results: Overall, among these 12 cell death pathways, 23, 47, and 549 genes were classified as always essential, partial essential, and rare essential, respectively. In two cell death pathways, Parthanatos, and Pyroptosis, all genes were rare essential. Among the other ten cell death pathways, Apoptosis, Autosis, Necroptosis, Efferocytosis, Ferroptosis, Mitotic cell death, Autophagy, Lysosome-dependent cell death, MPT-driven necrosis and Immunogenic, there are (10, 1, 13, 6, 3, 9, 11, 1, 1, 0) partial essential genes, and (2, 0, 3, 1, 1, 13, 4, 0, 0, 1) always essential genes. Conclusions: These cell death pathway essential genes could be viable targets for therapeutic drug development for cancer therapies.

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Cite This Study

Li et al. (2026) studied this question.

synapsesocial.com/papers/69e9bb2285696592c86ecf64https://doi.org/10.3390/genes17040491
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