Malignant Pleural Mesothelioma

Prospective, multi-institutional studies with standardized brain imaging are needed to further characterize the incidence of BrMs in DPM and associated risk factors. Routine brain surveillance at diagnosis and with symptoms should be considered for patients with DPM.

P1/2, N=126, Recruiting, Intergroupe Francophone De Cancerologie Thoracique | Not yet recruiting --> Recruiting

P3, N=825, Recruiting, AstraZeneca | Active, not recruiting --> Recruiting

P2/3, N=90, Recruiting, G.O.I.R.C. Gruppo Oncologico Italiano Di Ricerca Clinica | Not yet recruiting --> Recruiting

In addition, germline mutations are present in a subset of patients with mesothelioma and primarily involve genes in the DNA repair and cell cycle regulation and are more common in patients who are young, with family history of mesothelioma, or with peritoneal mesothelioma. In this review, we discuss the considerable heterogeneity of mesothelioma, the diversity of radiologic and gross presentation, various morphologic features with distinctive histologies and ultimately, we individually describe subsets of tumors characterized by uncommon alterations such as germline mutations, genomic near-haploidization, ALK rearrangement, ATF1 rearrangement, or EWSR1::YY1 fusion, as well as the implications of these findings on the diagnostic workup.

P=N/A, N=70, Not yet recruiting, University Hospital, Angers | Trial completion date: Oct 2027 --> Jun 2028 | Initiation date: Sep 2025 --> May 2026 | Trial primary completion date: Sep 2027 --> May 2028

Overexpression and chemotherapy-induced modulation of LDH-A and GLUT-1 correlated with poor MM prognosis. Combined inhibition of these two metabolic determinants impeded MM cell migration, stimulated ROS production and apoptosis, and affected spheroids' growth, offering promise for new treatment development.

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.

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.

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.