Mesothelioma

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

P2, N=31, Completed, Biotheus Inc. | Recruiting --> Completed | N=55 --> 31 | Trial completion date: Jun 2026 --> Mar 2026 | Trial primary completion date: Jun 2026 --> Mar 2026

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

About 20% of hepatobiliary carcinomas showed MTAP expression loss, which may benefit from MTAP-directed therapies. MTAP expression loss may be a diagnostic marker for malignant hepatobiliary tumors. MTAP-deleted CCAs and cHCC-CCAs may represent a distinct group of hepatobiliary tumors.

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.

The system was functionalized with two different anticancer drugs, doxorubicin or pemetrexed, using an on-demand release strategy based on a proteolytic sequence specifically recognized by metalloproteinase-9 (MMP-9), an enzyme overexpressed in various cancers. Based on these results, the platform was later tested on a more disease-specific model, the mesothelioma, to confirm its relevance and adaptability for treating this aggressive cancer. These findings suggest that EPA nanoparticles could serve as a promising drug delivery platform.

In addition, increased phosphorylation of AMPK and altered expression of mitochondrial oxidative phosphorylation (OXPHOS) complex proteins were associated with potential alterations in mitochondrial respiratory protein expression. Collectively, these findings suggest that QUE and ATG co-treatment is associated with increased apoptotic cell death in malignant mesothelioma cells in association with metabolic stress-related mitochondrial functional alterations.