Malignant Pleural Mesothelioma

EMT has been linked to the acquisition of a chemoresistant phenotype; moreover, the release of miRNAs into circulating exosomes from patients with MPM could also impact the resistance to conventional treatments. This review aims to summarize the current knowledge on the role of miRNAs in MPM and their relationship with chemoresistance, as well as to establish new knowledge to support the development of improved treatment for patients with MPM.

In patients with PD-L1 ≥ 1% and BAP1 loss, the median progression-free survival (mPFS) was numerically longer (10 vs. 7 months) but in patients with PD-L1 ≥ 1% and BAP1 positivity, PFS was statistically significantly shorter (1 vs. 7 months, p = 0.048). Our results did not show that PD-L1 and BAP1 are prognostic biomarkers for MPM, but positive PD-L1 expression and BAP1 loss were associated with worse survival in patients with MPM.

The pharmacological inhibition of AKT (ipatasertib), MEK (trametinib), and RSK (BI-D1870) resulted in the reversal of ROS-induced effects, with the strongest effects observed upon the inhibition of YB-1 phosphorylation by BI-D1870. The results suggest that ROS exposure has a strong impact on cell migration and immune evasion not only in PM cells but also in mesothelial cells, from which PM arises. Interfering with ROS-responsive kinase pathways, particularly YB-1 phosphorylation, could counteract pro-migratory and immune-evasive effects in PM.

P2, N=102, Completed, Bristol-Myers Squibb | Active, not recruiting --> Completed | Trial completion date: Oct 2026 --> Nov 2025 | Trial primary completion date: Oct 2026 --> Nov 2025

Finally, we show that high expression of PD-1 on circulating CD4+ T cells is an independent prognostic factor for poor survival in this patient group. This work suggests that MPE T cell phenotypes differ from those in circulation, with blood-based T cell subsets more sensitive predictors of outcome in this study.

The expression of tumor PD-L1 could serve as an adverse prognostic factor for PM patients. Its potential association with tumor stromal α-SMA expression warrants further investigation, particularly in the context of unmet needs in tumor immunotherapy.

P=N/A, N=30, Active, not recruiting, Istituto Romagnolo per lo Studio dei Tumori Dino Amadori IRST S.r.l. IRCCS | Recruiting --> Active, not recruiting | Trial completion date: Dec 2023 --> Nov 2026

P1, N=260, Recruiting, IDEAYA Biosciences | Not yet recruiting --> Recruiting

P2, N=41, Active, not recruiting, Istituto Oncologico Veneto IRCCS | Recruiting --> Active, not recruiting

Single biomarkers like miRNAs, mesothelin, and VOCs show promise, but further validation is needed in larger cohorts with correct control groups. A multi-omics approach, which integrates biomarker panels from various -omics areas, has the potential to enhance diagnostic accuracy.

The prominent conformation modifications of each complex during MD simulation has been determined via Markov state model confirms the stability of PLU-IPA in the binding site. These findings underscore the intricate molecular mechanisms underlying PM and highlight PLU-IPA as a potential therapeutic target for future investigations.

These include combination regimens with chemotherapy, radiotherapy, surgery, epigenetic modulators, anti-angiogenic agents, and novel immunotherapies such as next-generation checkpoint inhibitors (LAG-3, VISTA), immune-suppressive cell-targeting agents, vaccines, cell-based therapies, and oncolytic viruses. Collectively, these advancements underscore the importance of integrating histological classification with molecular and microenvironmental profiling to refine patient selection and guide the development of combination strategies aimed at transforming "cold" mesotheliomas into "hot," immune-responsive tumors, thereby enhancing the efficacy of ICB.