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Purpose of Review <p>BRCA1-associated protein 1 (<i>BAP1</i>) is a tumor suppressor gene involved in key cellular processes including DNA damage repair, cell cycle regulation, programmed cell death, and in the modulation of tumor microenvironment. The purpose of this manuscript is to describe the genomic features, structure, and biological functions of <i>BAP1</i>, as well as the clinical characteristics of patients with BAP1-mutated cancer. Moreover, we provide an updated overview of the main clinical trials testing the potential selective therapeutic strategies for BAP1-mutated cancer patients.</p> Recent Findings <p><i>BAP1</i> encodes for a ubiquitin hydrolase that binds to the ring finger domain of BRCA1 protein, modulating its function. While inactivating somatic and germline mutations in <i>BRCA1</i> are well-known to be involved in tumorigenesis, emerging studies have also demonstrated the role of BAP1 mutations in the pathogenesis of several malignancies such as uveal melanoma, malignant mesothelioma, and renal cell carcinoma. Notably, like BRCA1, inactivating BAP1 germline mutations define a tumor predisposition syndrome associated with an increased risk of early-onset hereditary malignancies. Moreover, tumors carrying germline or somatic mutations in BRCA1 have shown sensitivity to selective treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. Conversely, therapeutic options for cancer patients with BAP1 mutations, whether germline or somatic, still relies on non-selective treatments, so far. However, emerging lines of evidence suggested that BAP1-mutated tumors may also be susceptible to selective treatments, including PARP inhibitors.</p> Summary <p>BAP1 mutations confer a tumor predisposition syndrome analogous to BRCA1. Investigation of BAP1-driven cancers will advance precision treatment approaches for affected patients.</p>

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BRCA1-Associated Protein 1 (BAP1) in Human Cancer and its Emerging Role as a Novel Potential Therapeutic Target

  • 期刊论文

  • 发表日期：

    2026年2月20日

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  • Luigi Liguori,
  • Giovanna Polcaro,
  • Valentina Pagliara,
  • Rosario De Feo,
  • Giulia Cattaneo,
  • Marco Ventin,
  • Chiara Camillo,
  • Enrica Quattrocchi,
  • Maoyang Qi,
  • Liti Zhang,
  • Erica Daniels,
  • Eduardo Tejeda-Polanco,
  • Stefano Pepe,
  • Cristina R Ferrone,
  • Francesco Sabbatino

摘要

Purpose of Review

BRCA1-associated protein 1 (BAP1) is a tumor suppressor gene involved in key cellular processes including DNA damage repair, cell cycle regulation, programmed cell death, and in the modulation of tumor microenvironment. The purpose of this manuscript is to describe the genomic features, structure, and biological functions of BAP1, as well as the clinical characteristics of patients with BAP1-mutated cancer. Moreover, we provide an updated overview of the main clinical trials testing the potential selective therapeutic strategies for BAP1-mutated cancer patients.

Recent Findings

BAP1 encodes for a ubiquitin hydrolase that binds to the ring finger domain of BRCA1 protein, modulating its function. While inactivating somatic and germline mutations in BRCA1 are well-known to be involved in tumorigenesis, emerging studies have also demonstrated the role of BAP1 mutations in the pathogenesis of several malignancies such as uveal melanoma, malignant mesothelioma, and renal cell carcinoma. Notably, like BRCA1, inactivating BAP1 germline mutations define a tumor predisposition syndrome associated with an increased risk of early-onset hereditary malignancies. Moreover, tumors carrying germline or somatic mutations in BRCA1 have shown sensitivity to selective treatment with poly (ADP-ribose) polymerase (PARP) inhibitors. Conversely, therapeutic options for cancer patients with BAP1 mutations, whether germline or somatic, still relies on non-selective treatments, so far. However, emerging lines of evidence suggested that BAP1-mutated tumors may also be susceptible to selective treatments, including PARP inhibitors.

Summary

BAP1 mutations confer a tumor predisposition syndrome analogous to BRCA1. Investigation of BAP1-driven cancers will advance precision treatment approaches for affected patients.