Genome-wide CRISPR screen identifies BUB1 kinase as a druggable vulnerability in malignant pleural mesothelioma.

ABSTRACT: Malignant pleural mesothelioma (MPM) is a rare yet highly aggressive malignancy with a severe prognosis. Compounded by the lack of effective treatment modalities, MPM remains a formidable health challenge. Therefore, the identification of actionable liabilities is critical for advancing precision medicine to combat this lethal disease. Here, we exploit an unbiased genome-wide CRISPR screen, integrating and cross-comparing three MPM cell lines with nonmalignant mesothelial cells, to selectively map the gene targets whose depletion indicates a common dependency in MPM cells. This systematic approach unveils a cohort of verifiable genes, among which BUB1, a mitotic checkpoint serine/threonine kinase, emerges as a high-confidence hit in cancer cells. Cellular and molecular studies demonstrate

SUBMITTER: Cakiroglu E 

PROVIDER: S-EPMC11968822 | biostudies-literature | 2025 Apr

REPOSITORIES: biostudies-literature