Objectives: Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).
Materials And Methods: Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016-2018) MPM patients selected from the electronic databases of two ICC-of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1-line platinum/pemetrexed+/-antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.
Results: There were no differences in ORR or mPFS with CT between the groups: ORR-50% . 47% . 50% . 47% (p>0.9), mPFS-9.1mo (95% CI, 1.2-16.1) . 9.2mo (95% CI, 2.9-13.3) . 7.2mo (95% CI, 2.3-NR) . 10.9mo (95% CI, 2.9-20.3) (p>0.8) in groups A, B, B1, and B2, respectively. There were no differences in ORR or mPFS with ICPi between the groups: ORR-0% . 27% . 33% . 25% (p>0.2), mPFS-2.5mo (95% CI, 1.4-3.7) . 3.0mo (95% CI, 1.3-10.5) . 2.0mo (95% CI, 1.9-NR) . 4.5mo (95% CI, 0.3-10.5) (p>0.3) in groups A, B, B1, and B2, respectively. In group A, no responses were seen with PARPi; mPFS with PARPi was 1.8mo (95% CI, 1.8-NR). OSDx was 98.3mo (95% CI, 9.7-98.3) . 19.4mo (95% CI, 9.7-47.3) . 18.8mo (95% CI, 8.5-NR) . 19.5mo (95% CI, 8.3-82.2) in groups A, B, B1, and B2, respectively (p>0.3).
Conclusions: BAP1-altered MPM, as compared to non-selected MPM, is characterized by similar efficacy of CT and ICPi. Numerically longer OS in BAP1-altered MPM may reflect favorable tumor biology. No responses were observed with PARPi.
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http://dx.doi.org/10.3389/fonc.2021.603223 | DOI Listing |
Radiographics
March 2023
From the Department of Radiology, University of Texas Health at San Antonio, 7703 Floyd Curl Dr, San Antonio, TX 78229 (A.B., D.K., A.A., S.S., V.S.K.); Department of Radiology, Massachusetts General Hospital, Boston, Mass (R.S.); Departments of Radiology (S.R.P.) and Pathology (N.R.), University of Texas M. D. Anderson Cancer Center, Houston, Tex; Department of Radiology, NYU Medical Center, New York, NY (K.S.); and Department of Radiology, University of Pittsburgh Medical Center, Pittsburgh, Pa (A.K.D.).
A diverse spectrum of benign entities and malignant neoplasms originate from the monotonous mesothelium that lines the serosal membranes of the pleural, pericardial, and peritoneal cavities. The mesothelium of myriad sites shows a common origin from the lateral plate mesoderm; primary mesothelial tumors thus demonstrate similar pathogenesis, imaging findings, and treatment options. Significant changes have been made in the 2021 World Health Organization (WHO) classification schemata of the pleural and pericardial tumors on the basis of recent advances in pathology and genetics.
View Article and Find Full Text PDFMol Cancer Res
May 2023
Molecular Physiology and Cell Signalling, University of Liverpool, Liverpool, United Kingdom.
Unlabelled: The nuclear deubiquitylase BRCA1-associated protein 1 (BAP1) is frequently inactivated in malignant pleural mesothelioma (MPM) and germline BAP1 mutation predisposes to cancers including MPM. To explore the influence on cell physiology and drug sensitivity, we sequentially edited a predisposition mutation (w-) and a promoter trap (KO) into human mesothelial cells. BAP1w-/KO MeT5A cells express less BAP1 protein and phenocopy key aspects of BAP1 loss in MPM.
View Article and Find Full Text PDFPigment Cell Melanoma Res
January 2022
Department of Cancer Biology, Thomas Jefferson University, Philadelphia, PA, USA.
Metastatic uveal melanoma (UM) responds poorly to targeted therapies and immune checkpoint inhibitors. Loss of BRCA1-associated protein 1 (BAP1) via inactivating mutations in the BAP1 gene is associated with UM progression. Thus, molecular alterations caused by BAP1 dysfunction may be novel therapeutic targets for metastatic UM.
View Article and Find Full Text PDFFront Oncol
March 2021
Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
Objectives: Little is known regarding the outcomes of systemic treatments in BAP1-altered malignant pleural mesothelioma (MPM).
Materials And Methods: Forty five patients with MPM [group A: eight MPM patients with BAP1 inactivating mutation/copy number loss (FoundationOne CDx/TEMPUSxT), selected from the electronic databases of four Israeli cancer centers (ICC); group B: 37 consecutive (years 2016-2018) MPM patients selected from the electronic databases of two ICC-of those six patients without a BAP1 alteration (group B1) and 31 patients not tested for BAP1 (group B2)] were analyzed for ORR, PFS (mRECIST), and OS with 1-line platinum/pemetrexed+/-antiangiogenic drug (CT, n-28), immune check-point inhibitors (ICPi, n-16) and poly (ADP-ribose) polymerase inhibitors (PARPi, n-4). OS since diagnosis (OSDx) was assessed.
Cancer Treat Rev
November 2020
Center for Personalized Cancer Therapy, University of California San Diego, Moores Cancer Center, 3855 Health Sciences Dr, La Jolla, CA 92037, USA.
BRCA1-Associated Protein 1 (BAP1) is a ubiquitin carboxy-terminal hydrolase that has been established as a tumor suppressor, utilizing its deubiquitinating activity to regulate a number of processes including DNA damage repair, cell cycle control, chromatin modification, programmed cell death, and the immune response. Mutations in the BAP1 gene commonly result in a number of aggressive cancers; predominantly uveal melanoma, malignant mesothelioma, renal cell carcinoma, and cutaneous melanoma. Importantly, germline mutations in the BAP1 gene have been established as a novel tumor predisposition syndrome, conferring an increased risk of hereditary, early-onset cancers.
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