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.
© 2026. The Author(s), under exclusive licence to Springer Nature Limited.