Malignant Pleural Mesothelioma

Trop-2 was expressed in 20% of PMs, exclusively in epithelioid histology, associated with advanced disease and poor survival outcomes. These results support the prospective evaluation of Trop-2-targeted therapies in PM.

Importantly, these cells display a favorable safety profile, with minimal evidence of graft-versus-host disease, cytokine release syndrome, brain infiltration or neurotoxicity, and no detectable off-tumor effects. Collectively, these findings support the development of a clinically translatable, off-the-shelf CAR-NKT cell therapy for the treatment of MPM.

One case harbored an ALK rearrangement, guiding effective targeted therapy with alectinib...Accurate histopathological assessment is essential to establish a correct diagnosis and guide appropriate therapy. A multidisciplinary approach remains the cornerstone of diagnostic precision in CUP cases.

Finally, this cascade triggers immunogenic cell death and orchestrates a chemokine storm, which is hypothesized to facilitate the conversion of the tumor microenvironment from an immune "cold" to a "hot" phenotype. Collectively, by integrating the physical disintegration of subcellular structures with immunological remodeling, TTFields may offer a hypothetical theoretical framework for overcoming therapeutic resistance in MPM.

P1, N=74, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Jun 2026 --> Jun 2027 | Trial primary completion date: Jun 2026 --> Jun 2027

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.