Malignant Pleural Mesothelioma

Longitudinal changes in SMRP levels corresponded with a radiographic presence of disease in a subset of patients. SMRP surveillance could aid in detection of local recurrences, whereas CA-125 could be helpful in recognizing abdominal recurrences.

Given the limited effectiveness of current treatments, targeting the YAP/TAZ-TEAD signalling cascade has emerged as a promising therapeutic strategy in MPM. Several inhibitors of the YAP/TAZ-TEAD signalling axis are presently undergoing clinical development, with the goal of advancing them to clinical use in the near future.

P1, N=198, Recruiting, Ikena Oncology | Trial completion date: Oct 2024 --> Jun 2025 | Trial primary completion date: Oct 2024 --> Jun 2025

P1/2, N=126, Not yet recruiting, 7 Hills Pharma, LLC

Immunohistochemistry markers are essential in accurately diagnosing malignant pleural mesothelioma and its histological subtypes. This systematic review and meta-analysis provide a comprehensive insight into the diagnostic performance of these markers, facilitating their potential clinical utility in the discrimination of malignant pleural mesothelioma from other pleural pathologies and the differentiation of malignant pleural mesothelioma subtypes.

P=N/A, N=200, Recruiting, Mayo Clinic | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=200, Recruiting, Mayo Clinic | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P=N/A, N=200, Recruiting, Mayo Clinic | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2023 --> Dec 2024

P1/2, N=117, Active, not recruiting, National Cancer Institute (NCI)

This is the first study of its kind to establish long-term mesothelioma organoid cultures from malignant pleural effusions and report on their utility to test individuals' chemotherapeutic sensitivities ex vivo.

Our findings indicate immune checkpoint and/or immune cell-targeting therapies against CD70-CD27 and/or CD47-SIRPA axes may be applied for PM patients in combination with PD-L1-PD-1 targeting therapies in accordance with their tumor immune microenvironment characteristics.

We also discovered the SKA3-DDX10 fusion in two MPM genomes, which is a novel finding for MPM. We found that MPM genomes are very complex, suggesting that this highly rearranged pattern is strongly related to driver mutational status like BAP1, TP53 and RB1.

P2, N=25, Not yet recruiting, Hyogo Medical University

Once PEHE is suspected in histology it can be confirmed with immunohistochemistry. Chemotherapy, surgery or a combination of both is currently used as the treatment but the standard treatment remains a question.

P2, N=63, Not yet recruiting, Oncotelic Inc. | Trial completion date: Dec 2026 --> Dec 2029 | Trial primary completion date: Dec 2025 --> Dec 2028

P1/2, N=100, Active, not recruiting, University Health Network, Toronto | Trial completion date: Sep 2023 --> Sep 2024 | Trial primary completion date: Sep 2023 --> Sep 2024

To this end, we report on the role of deubiquitinase BRCA1-associated protein-1 (BAP1), a tumour suppressor gene with a widely acknowledged role in the corrupted signalling and metabolism of PMe. This review aims to enhance our understanding of this devastating malignancy and propel efforts for its investigation.

P1/2, N=36, Active, not recruiting, TCR2 Therapeutics | Recruiting --> Active, not recruiting | N=175 --> 36 | Trial completion date: Apr 2026 --> Nov 2028 | Trial primary completion date: Jul 2024 --> Nov 2028

P1/2, N=6, Active, not recruiting, TCR2 Therapeutics | Trial completion date: Dec 2027 --> Oct 2028 | Trial primary completion date: Nov 2023 --> Oct 2028

POLD1 plays essential roles in overcoming DNA damage and cell cycle progression at the G1/S checkpoint in MPM cells. These findings suggest that POLD1 may be a novel therapeutic target in MPM.

The three lncRNAs showed great potential as independent predictive diagnostic biomarkers. Although the prediction model for MALAT1 did not significantly differ, MALAT1 was significantly expressed in patients more than in controls (p = 0.0266), and the recorded sensitivity and specificity were greater than those of GAS5.

P2, N=118, Active, not recruiting, Åslaug Helland | Trial primary completion date: Mar 2024 --> Mar 2025

Among these genes responsible for collagen formation, COL1A1 and COL5A1 exhibited elevated expression, suggesting changes in matrix stiffness. Overall, our data show that primary mesothelioma cells can be effectively expanded in Nichoids and that 3D growth affects the cells' tensegrity or the mechanical stability of their structure.

Survival after recurrence was also significantly improved by CHST4 expression. These results suggest that CHST4 is useful as a prognostic biomarker in MPM.

MPMs in individuals with these variations are less severe, and their medical care necessitates a collaborative effort. Additionally, we have outlined the current therapeutic prospects for MPM, including the possibility of gene-specific therapy, which is currently promising but still requires clinical validation.

Based on our systematic literature review there is suggestive evidence that the expression of specific miRNAs in the blood serum or plasma are associated with asbestos-related LC and MPM diagnosis and prognosis. Further large longitudinal studies are urgently needed to validate these findings and elucidate the underlying mechanisms given the potential important implications for patients' survival.

P3, N=480, Active, not recruiting, University of Sydney | Recruiting --> Active, not recruiting

P1, N=22, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=35 --> 22

Combination treatment with X-ray irradiation and gemcitabine (as a radiosensitizer) strongly suppressed the growth of BAP1-deficient cells. Our results suggest reciprocal positive interactions between BAP1 and DNA-PKcs, based on phosphorylation of BAP1 by the latter and deubiquitination of DNA-PKcs by BAP1. Thus, functional interaction of BAP1 with DNA-PKcs supports a role for BAP1 in NHEJ DNA repair and may provide the basis for new therapeutic strategies and new insights into its role as a tumor suppressor.

P2, N=38, Recruiting, Sun Yat-sen University | Initiation date: Jul 2023 --> Nov 2023 | Not yet recruiting --> Recruiting

P1/2, N=115, Recruiting, Medicenna Therapeutics, Inc. | Trial primary completion date: Sep 2024 --> Jun 2026

MTB advised molecular-guided treatment options in 32 situations, for 17 PM and 15 TET patients (75% clinical trial option, 22% off-label drug or compassionate use, 3% early access program). Molecular testing and MTB discussion were feasible for patients with rare thoracic cancers and allowed the broadening of treatment options for 30% of the cases.

P2, N=140, Recruiting, M.D. Anderson Cancer Center | Trial completion date: Apr 2024 --> Apr 2025 | Trial primary completion date: Apr 2024 --> Apr 2025

P1, N=240, Recruiting, Inhibrx, Inc. | Trial completion date: Dec 2024 --> Jul 2026 | Trial primary completion date: Aug 2024 --> Dec 2025

Fluorescence in situ hybridization, DNA and RNA next-generation sequencing showed no mesothelioma-associated tumour suppressor gene mutations, but deletion of CDKN2A and a rare TFG-ADGRG7 fusion both reported in pleural mesotheliomas, were detected. Clinicians should consider malignancy in case of discrepancy between symptoms and objective findings in scrotal conditions.

However, treatment efficacy varies greatly from case to case, and no biomarkers have been developed to accurately predict efficacy. In this article, we discuss the past and future of ICI therapy for lung cancer, based on clinical and basic evidence accumulated to-date.

The IHC biomarkers BAP1, WT1, and calretinin, used in the routine diagnosis of PM and their combinations, are the first biomarkers associated with response to chemotherapy and may be a useful tool to select patients for first-line platinum pemetrexed treatment in PM patients. Validation in a large cohort is ongoing.

P=N/A, N=30, Recruiting, Hospices Civils de Lyon | Not yet recruiting --> Recruiting

A 3D cell culture model based on MSLN-expressing multicellular tumor spheroids reveals NA penetration in the first superficial layers. Altogether, these results open the path to novel anticancer strategies based on MSLN-activated internalization of NA incorporating drugs to promote specific accumulation of active treatments in tumors.

P2, N=34, Active, not recruiting, H. Lee Moffitt Cancer Center and Research Institute | Trial completion date: Dec 2023 --> Dec 2024

It has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.

P2, N=68, Active, not recruiting, Swiss Group for Clinical Cancer Research | Trial completion date: Sep 2024 --> May 2024 | Trial primary completion date: Sep 2024 --> May 2024