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<p>Mesothelioma is an aggressive cancer that is often characterized by loss of the <i>BRCA1-associated protein 1</i> (<i>BAP1</i>) tumor suppressor gene. This alteration typically occurs as an early clonal event in mesothelioma development, making it a promising candidate for both diagnostic and therapeutic applications. Functionally, BAP1 regulates gene expression through interactions with Polycomb-group complexes, and it plays roles in various other cellular processes including DNA repair, replication stress, and cell metabolism. While preclinical research has identified multiple potential vulnerabilities in <i>BAP1</i>-deficient tumors—including sensitivity to EZH2-, HDAC-, PARP-, and FGFR-inhibitors—translating these findings to the clinic remains a challenge. In this review, we provide a comprehensive overview of BAP1’s molecular functions in mesothelioma, with a focus on their translation into clinical therapeutics for this hard-to-treat malignancy.</p>

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BAP1-loss in mesothelioma: molecular mechanisms and clinical opportunities

  • 期刊论文

  • 发表日期：

    2026年1月7日

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  • Jasper H.L.T. van Genugten,
  • Dean A. Fennell,
  • Paul Baas

摘要

Mesothelioma is an aggressive cancer that is often characterized by loss of the BRCA1-associated protein 1 (BAP1) tumor suppressor gene. This alteration typically occurs as an early clonal event in mesothelioma development, making it a promising candidate for both diagnostic and therapeutic applications. Functionally, BAP1 regulates gene expression through interactions with Polycomb-group complexes, and it plays roles in various other cellular processes including DNA repair, replication stress, and cell metabolism. While preclinical research has identified multiple potential vulnerabilities in BAP1-deficient tumors—including sensitivity to EZH2-, HDAC-, PARP-, and FGFR-inhibitors—translating these findings to the clinic remains a challenge. In this review, we provide a comprehensive overview of BAP1’s molecular functions in mesothelioma, with a focus on their translation into clinical therapeutics for this hard-to-treat malignancy.