Mesothelioma

P2, N=257, Recruiting, AstraZeneca | N=110 --> 257

Young patients with DPM have strong personal and family histories of cancer, and heterogeneous somatic and germline alterations, indicating divergent underlying biology. With the increasing prevalence of young adults with cancers, mesotheliomas, although uncommon, should be on the differential for patients even without asbestos exposure history in this age group.

P2, N=0, Withdrawn, National Cancer Institute (NCI) | N=15 --> 0 | Trial completion date: Dec 2027 --> Mar 2026 | Not yet recruiting --> Withdrawn | Trial primary completion date: Dec 2027 --> Mar 2026

In this large PM cohort,CDKN2A, NF2, and TP53 alterations were associated with worse OS, while BAP1 alterations were associated with better prognosis, independent of clinical variables and histology. Modeling suggests that genomic alterations provide additional prognostic information beyond anatomic TNM and clinicopathologic features.

We see recurrent somatic mutations in MCMs particularly at a novel mutational hotspot in SMC3, consistent with a neoplastic process. Mutations in cohesin complex genes are associated with disease recurrence.

Data obtained clearly highlighted how TGF-β inhibition, through the silencing or treatment of MPM cells with antibody anti-TGF-β (Fresolimumab), significantly reduces cell proliferation (MTT, PCNA) and prevents metastasis, reducing EMT and decreasing the invasiveness and migration of MPM cells...Taken as a whole, targeting TGF-β will represent a starting point for future improvements in MPM management. This is particularly important as we foresee a growing increase in MPM in the coming years.

Although tissue-agnostic therapy has expanded the reach of precision oncology, thoracic and H&N cancers remain underrepresented in registrational evidence. Most approvals rely on single-arm basket studies with small, heterogeneous subsets that preclude histology-specific conclusions. Future research should prioritize histology-enriched trial designs, standardized molecular diagnostics, and real-world validation to establish reliable, equitable standards of care for these underrepresented malignancies.

P1, N=7, Active, not recruiting, Memorial Sloan Kettering Cancer Center | Recruiting --> Active, not recruiting | N=14 --> 7

P1/2, N=49, Active, not recruiting, National Cancer Institute (NCI) | Trial completion date: Sep 2026 --> Feb 2027

These findings demonstrate O-GlcNAcylation-driven enhancement of nuclear export as a therapeutically actionable vulnerability in mesothelioma with inactivation of the Hippo pathway.

P1, N=24, Active, not recruiting, M.D. Anderson Cancer Center | Trial completion date: Dec 2025 --> Dec 2028

P1/2, N=104, Completed, University Health Network, Toronto | Active, not recruiting --> Completed | Trial completion date: Sep 2027 --> Sep 2025 | Trial primary completion date: Sep 2027 --> Sep 2025