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BAP1 Mutations and Pleural Mesothelioma: Genetic Insights, Clinical Implications, and Therapeutic Perspectives
Susana Cedres1, Augusto Valdivia1, Ilaria Priano1
1Medical Oncology Department, Vall d'Hebron Institute of Oncology (VHIO), Vall d'Hebron Hospital Universitari, Paseo Vall d'Hebron 119, 08035 Barcelona, Spain.
Abstract:
Pleural mesothelioma (PM) is a locally aggressive tumor associated with asbestos exposure. Despite legislative efforts to regulate asbestos use, its incidence continues to rise in some parts of the world. Chemotherapy and immunotherapy have improved survival in PM patients, but overall survival remains poor. Molecular analysis of PM patients has shown that most alterations occur in tumor suppressor genes, with BAP1 being the most frequently affected. Patients with germline BAP1 mutations have been reported to have a better prognosis, but this is not observed in those with somatic mutations. Interest in developing drugs targeting patients with BAP1 loss has led to several phase II studies in recent years. Unfortunately, initial results have not been very promising. In this review, we conclude that, at this time, with the contradictory results from studies and the limited number of patients evaluated, BAP1, the most commonly altered gene in PM, is not yet suitable for use in clinical practice as a prognostic or predictive factor. Future studies are needed to establish the prognostic or predictive value of BAP1.
Insights
Pleural mesothelioma (PM) is a cancer linked to asbestos. While BAP1 gene alterations are common in PM, its use as a clinical factor is not yet supported by current research.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Pleural mesothelioma (PM) is an aggressive malignancy primarily caused by asbestos exposure.
- Despite regulatory efforts, PM incidence is increasing globally.
- Current treatments offer limited survival benefits, necessitating novel therapeutic strategies.
Purpose of the Study:
- To review the role of the BAP1 gene in pleural mesothelioma.
- To evaluate the prognostic and predictive value of BAP1 alterations in PM patients.
- To assess the potential of BAP1 as a therapeutic target.
Main Methods:
- Comprehensive literature review of studies investigating BAP1 in PM.
- Analysis of clinical trial data and molecular profiling of PM patients.
- Evaluation of BAP1 mutation status in relation to patient prognosis and treatment response.
Main Results:
- BAP1 is the most frequently altered tumor suppressor gene in PM.
- Germline BAP1 mutations may correlate with better prognosis, unlike somatic mutations.
- Targeted therapies for BAP1-deficient PM have shown limited success in early-phase trials.
Conclusions:
- BAP1 is a significant molecular alteration in PM but lacks established prognostic or predictive value.
- Contradictory findings and limited patient data preclude current clinical application of BAP1.
- Further research is essential to determine the definitive role of BAP1 in PM management.
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