Malignant Pleural Mesothelioma

P3, N=861, Active, not recruiting, AstraZeneca | Recruiting --> Active, not recruiting | Trial primary completion date: Nov 2027 --> Nov 2028

For nearly twenty years, platinum-pemetrexed chemotherapy has persisted as the unchanged standard treatment; although recent progress in immunotherapy has modestly disrupted this therapeutic plateau, survival outcomes remain disappointingly limited...Preclinical and early clinical data demonstrate that EZH2 inhibitors-including tazemetostat, valemetostat, GSK126, EPZ011989, tulmimetostat, and novel PROTAC-based degraders such as MS1943-can suppress tumor progression, modulate the tumor immune microenvironment, and restore therapeutic sensitivity...Further understanding the dual canonical and non-canonical roles of EZH2 in tumor biology will be key to optimizing targeted and combinatorial treatment strategies. Future research should focus on translating EZH2 inhibition into clinical benefit, identifying predictive biomarkers of response, and exploring rational combinations with chemotherapy, targeted drugs, or immunotherapy to improve survival outcomes in mesothelioma patients.

PTPA promotes oncogene-induced senescence (OIS) in MPM. By preventing OIS, heterozygous PTPA loss may contribute to mesothelial transformation and carboplatin resistance.

P1/2, N=15, Recruiting, University Hospital, Antwerp | Trial completion date: Oct 2026 --> Oct 2027 | Trial primary completion date: Oct 2026 --> Oct 2027

P2, N=30, Active, not recruiting, Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins | Trial completion date: Jun 2027 --> Jun 2028 | Trial primary completion date: Jun 2026 --> Jun 2027

The patient received adjuvant chemotherapy and remained free of disease at 11 months of follow-up. This report expands the histomorphologic and molecular spectrum of paratesticular mesothelioma with the novel identification of a BRAF V600E mutation.

Mesothelioma can rarely present with dominant esophageal involvement. Awareness of this atypical presentation facilitates timely diagnosis, appropriate management, and may prevent diagnostic delays in patients presenting with dysphagia.

Our study uncovers a previously unknown mechanism of resistance to immunotherapy by identifying the dynamic interplay between cancer cell genetic alterations and the TIME.

Our findings demonstrate that mesothelioma therapeutic escape is not a uniform process. Identifying these patient-specific metabolic and transcriptomic trajectories via 3D PDOs provides a hypothesis-generating framework to explore potential avenues for future personalised therapy.

P1, N=25, Completed, M.D. Anderson Cancer Center | Active, not recruiting --> Completed | Trial completion date: Dec 2028 --> Apr 2026

In conclusion, TLR9 expression is significantly elevated in epithelioid mesothelioma compared to MLAC at both the molecular and cellular levels, and its expression correlates with increased tumor proliferation and poorer prognosis. Our data suggest that TLR9 could represent a promising diagnostic and prognostic biomarker, warranting further investigation into its potential therapeutic applicability.

MIS is a challenging diagnosis that requires close integration of clinical, radiological, and pathological data. Recognition of this entity may allow earlier identification of patients at risk of invasive mesothelioma. Our findings primarily illustrate the heterogeneity of MIS-spectrum lesions and the importance of adequate tissue sampling and longitudinal follow-up. Larger prospective studies are needed to clarify its natural history, validate prognostic molecular markers, and define optimal surveillance and treatment approaches.