Malignant Pleural Mesothelioma

Collectively, these findings reveal a previously unknown mechanism of action of ecteinascidins that merits further investigation for potential clinical applications in the treatment of MPM, as new first line treatment in monotherapy or in association with immunotherapy.

No abstract available

P=N/A, N=200, Recruiting, Mayo Clinic | Trial completion date: Dec 2024 --> Dec 2025 | Trial primary completion date: Dec 2024 --> Dec 2025

ΔT2 values increased over 4 weeks, correlating strongly with PD-L1 expression (P < 0.05). The PD-L1-targeted nanoprobe with MRI is a promising tool for noninvasive, real-time assessment of PD-L1 expression in MPM.

Patients with pleural mesothelioma treated with nivolumab and ipilimumab with or without UV1 vaccine in the NIPU study were included. Elevated levels of certain cytokines, both before and after onset of treatment, correlate with specific irAEs in PM patients receiving ICIs. These cytokines may be used as biomarkers to predict and detect irAES.

ILK showed no prognostic value. Further studies with larger cohorts are needed to identify prognostic and predictive biomarkers facilitating optimized individual treatment decision in this rare type of cancer.

This proof-of-concept work demonstrated the potential of radiomics to differentiate among BAP1+/- in patients with PM. Future work will extend these methods to the assessment of germline BAP1 mutation status through image analysis for improved patient prognostication.

Moreover, all four miRNAs (hsa-miR-181a-2-3p, hsa-miR-491-5P, hsa-miR-503-5p, and hsa-miR-3934-5p) were found to be differentially expressed in PM cell lines as compared with normal cell line, GO and KEGG analysis revealed that target genes of miRNAs in prognostic model were involved in multiple tumor-associated signaling pathways and functions in PM, core miRNA targets also correlated with immune cell infiltration, indicating their potential role in PM initiation and progression. A robust four-miRNA prognostic signature with great performances in prediction of the OS for PM patients was developed in our study, providing new avenues for the prognostic predication of PM.

This study confirmed that FE exposure promotes the onset of fibrotic lesions at pleural level, as fibrous plaques or nodules and fibrosis, through a mechanism similar to other form of asbestos. These results combined with epidemiological study reported in Biancavilla residents, corroborate the need to promote health and epidemiological surveillance plans of respiratory diseases in population living in FE contaminated sites.

P2, N=52, Active, not recruiting, Abramson Cancer Center at Penn Medicine | Recruiting --> Active, not recruiting | N=102 --> 52

P2/3, N=520, Completed, Canadian Cancer Trials Group | Active, not recruiting --> Completed | Trial completion date: Jun 2024 --> Oct 2024 | Trial primary completion date: Apr 2023 --> Oct 2024

DNA methylation analyses provide a robust method for distinguishing PM from healthy pleural tissues, and specific methylation patterns exist within PM subtypes. These methylation differences underscore their importance in understanding disease progression and may serve as viable biomarkers or therapeutic targets. Moreover, differential methylation patterns between PM and other lung cancers highlights its diagnostic potential. These findings necessitate further translational studies to explore their clinical applications.

Furthermore, patients who received 1L platinum/pemetrexed chemotherapy are often considered for second or further-line (2L+) ipi-nivo on the basis of MAPS2 results. The highest-grade TRAE was 1 to 2 in 58% of these patients and 3 or higher in 42% Treatment discontinuation due to a TRAE occurred in 22% of patients. In this real-world cohort of patients with MPM treated with ipi-nivo survival outcomes were inferior to those reported in the CheckMate-743 and MAPS2 trials, whereas safety outcomes were similar.

P1, N=10, Completed, Memorial Sloan Kettering Cancer Center | Active, not recruiting --> Completed | Trial completion date: Jul 2025 --> Nov 2024 | Trial primary completion date: Jul 2025 --> Nov 2024

P1, N=67, Terminated, Ikena Oncology | N=198 --> 67 | Trial completion date: Jun 2025 --> Sep 2024 | Active, not recruiting --> Terminated | Trial primary completion date: Jun 2025 --> Aug 2024; Sponsor strategic reasons

NOTCH2 and PTP4A3 alterations are associated with clinical outcomes in pemetrexed-treated PM patients. The inhibition of NOTCH pathway may be exploited to eradicate CSCs and improve patients' survival.

Our findings demonstrate the utility of the interactome in uncovering biological associations and in generating clinically translatable results.

In this particular case, treatment with crizotinib demonstrated some initial efficacy, which suggests that this might be a promising strategy for patients with advanced MPM with an ALK gene mutation. This required further research and evaluation in the future.

P2, N=40, Recruiting, Istituto Oncologico Veneto IRCCS | Not yet recruiting --> Recruiting

P3, N=53, Active, not recruiting, Ferring Ventures Limited | Trial completion date: Nov 2024 --> Apr 2026 | Trial primary completion date: Nov 2023 --> Mar 2024

P2, N=58, Active, not recruiting, The Netherlands Cancer Institute | Trial completion date: Mar 2025 --> Mar 2026

The International Mesothelioma Interest Group recommends using at least 2 mesothelial markers, such as calretinin, WT1, CK5/6 or D2-40, and 2 epithelial markers, such as claudin-4, CEA, MOC-31, as well as a broad-spectrum cytokeratin stain (AE1/AE3) as part of an initial immunohistochemical panel. Metastatic mesothelioma should be included in the differential diagnosis of malignant epithelioid dermal tumors with unusual staining patterns.

This study characterized CD146 expression and binding/internalization kinetics of the CD146-targeting antibody OI-3 coupled with 212Pb (212Pb-TCMC-OI-3) in human mesothelioma cells...The ability of 212Pb-TCMC-mOI-3 to target and inhibit the growth of intraperitoneal mesothelioma xenografts supports targeted radionuclide therapy's efficacy for metastatic peritoneal mesothelioma. This study highlights the potential of localized CD146-targeted radioimmunotherapy for malignant mesothelioma, offering a new avenue for improving patient outcomes.

P2, N=106, Terminated, Sanofi | Active, not recruiting --> Terminated; Early discontinuation based on strategic sponsor decision not driven by any safety concerns.

HPD is a mode of progression for ICI-treated PM patients. Further investigation is needed to better define and anticipate HPD in these patients.

Distinct differences in the T cell immune infiltrates in mesothelioma are strongly associated with overall survival. The tumor microenvironment could therefore serve as a source of prognostic biomarkers.

Radiation therapy, immunotherapy, chemotherapy, and surgery are some of the treatment options that are currently available. This systematic review provides a comprehensive analysis of the latest research, biomarkers, evaluation, and management strategies for malignant pleural mesothelioma.

P1/2, N=49, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2024 --> Sep 2025

P=N/A, N=52, Recruiting, Centro di Riferimento Oncologico - Aviano

SMRP is a promising serum biomarker for predicting survival in MPM patients treated with ICT and warrants prospective investigation.

Compared with the control group, the expression levels of Vimentin, Twist and E-cadherin genes in chrysotile group were increased, while the expression levels of hsa-miR-34b-5p, hsa-miR-34c-5p and hsa-miR-28-5p were decreased (P<0.05) . Long-term exposure to chrysotile and crocidolite could cause Met-5A cells to produce miRNAs and EMT-related gene expression changes similar to mesothelioma cells.

By integrating genomic analysis with a series of in vitro and in vivo functional studies, we validate and prioritize several non-oncogene addictions conferred by CDK7, CHK1, HDAC3, RAD51, TPX2, and UBA1 as targetable vulnerabilities, revealing previously unappreciated aspects of PM biology. Our findings support the growing consensus that stress-responsive non-oncogenic signaling plays a key role in the initiation and progression of PM and provide a functional blueprint for the development of unprecedented targeted therapies to combat this formidable disease.

P2, N=41, Completed, Sellas Life Sciences Group | N=31 --> 41

Moreover, the adeno-associated virus serotype 6 (AAV6) has been engineered to deliver both NF2 and SuperHippo genes into mesothelial cells, which substantially impedes tumor growth in xenograft and genetic DPM models and prolongs the median survival of mice. These findings serve as a proof of concept for the potential use of gene therapy targeting the Hippo pathway to treat DPM.

With its emergence as a predictive biomarker, the implementation of MTAP IHC into diagnostic routine for NSCLC and other tumors is likely to take place soon. In this review article, we summarize the current literature on the role of MTAP in thoracic tumors and evaluate different testing methods, including IHC, FISH and next generation sequencing.

P1/2, N=91, Recruiting, NuCana plc | Trial primary completion date: Aug 2024 --> Jan 2025

The combination of nivolumab and ipilimumab-based immunotherapy outperformed platinum and pemetrexed-based chemotherapy in terms of survival benefit and improved quality of life especially for non-epithelioid subtypes. This review article provides an overview of epidemiology, etiology, clinical manifestations, diagnostic approaches (including immunohistochemical and genetic markers), staging, and multidisciplinary approaches to current treatment for malignant pleural mesothelioma using surgery, chemotherapy, immunotherapy, and radiotherapy. It also sheds light on some recent studies (EMPHACIS, CALGB30901, Checkmate-743, etc.) that have led to significant developments in recent years with clinically meaningful results.

Furthermore, when we tested Neratinib (an inhibitor of MAD2L1) and iMDK (an inhibitor of MDK) we found that they are effective on MPM cells, in part phenocopying the effects of MAD2L1 and MDK gene silencing. In summary, in the present work, we report that BAG2, MAD2L1, and MDK are bona fide cancer-driver genes for MPM worth of further studies.

Notably, high LAT1 expression proved to be a significant predictor of outcome, particularly in the subgroup with high PLR and SII. LAT1 was a significant predictor of outcomes in patients with PM and was more predictive of worse outcomes in patients with high inflammatory and low nutritional status.

P2, N=40, Not yet recruiting, Istituto Oncologico Veneto IRCCS | Trial completion date: Dec 2026 --> Mar 2027 | Initiation date: Jun 2024 --> Oct 2024 | Trial primary completion date: Jun 2026 --> Mar 2026

P1/2, N=56, Active, not recruiting, Aminex Therapeutics, Inc. | Suspended --> Active, not recruiting

P1, N=5, Active, not recruiting, Roswell Park Cancer Institute | Suspended --> Active, not recruiting | N=16 --> 5 | Trial completion date: Mar 2025 --> Jan 2026 | Trial primary completion date: Mar 2025 --> Feb 2024