Mesothelioma

P=N/A, N=300, Completed, Mansoura University Hospital

P1, N=12, Terminated, M.D. Anderson Cancer Center | Trial completion date: Dec 2027 --> Feb 2026 | Active, not recruiting --> Terminated | Trial primary completion date: Dec 2027 --> Feb 2026; <75% participation

Increases of CD45+ and CD8+ T-cell infiltrates, as well as CD8+ T-cell activation, observed in xenograft tumor tissues were time and JNJ-79032421 dose dependent. Overall, these data suggest that JNJ-79032421 may offer meaningful clinical activity by avoiding binding to sMSLN.

P1, N=10, Not yet recruiting, Allegheny Singer Research Institute (also known as Allegheny Health Network Research Institute)

Our drug screening assay showed that the fatty acid synthase (FASN) inhibitor cerulenin demonstrates strong and selective antiproliferative properties against NF2/CDKN2A(p16)-deficient PM cells, surpassing the effects of C75, cisplatin or pemetrexed. These findings suggest that FASN might play a role in the tumorigenesis of PM cells through the regulation of mitochondrial dynamics. This research offers a novel perspective on the potential development of precision medicine for PM.

Moreover, TTFields-induced tumor immunogenicity may enable combination strategies with immunotherapies. A phase 2 clinical trial investigating TTFields with Gem/NabP and immune checkpoint inhibitors (ICIs) for metastatic PDAC is currently underway.

These alterations provide potential targets for ongoing early-phase clinical trials. Future advances in PM will depend on the development and integration of comprehensive biomarker models that combine clinicopathologic, immune, and molecular features of this complex and heterogenous disease.

Immunotherapy has significantly reshaped the management of malignant pleural mesothelioma (MPM), offering new therapeutic opportunities after decades in which platinum-pemetrexed chemotherapy represented the only systemic option...Evidence from monotherapy trials has been inconsistent, whereas combination approaches-particularly nivolumab plus ipilimumab-have demonstrated improved survival compared with chemotherapy, mainly in non-epithelioid tumors...Overall, current evidence suggests that sensitivity to immunotherapy in MPM arises from a complex interplay of genomic, immunologic, and clinical factors, and that no biomarker is yet suitable for guiding treatment decisions. Prospective studies integrating molecular and immune profiling will be essential to refine patient selection and advance toward a more rationally personalized use of immunotherapy.

A combination of defactinib and the MDM2 inhibitors showed that nutlin-3a showed synergistic/additive effects in wild-type and antagonistic effects in mutated TP53 cells, whereas RITA retained synergistic activity in mutated TP53 cells. These results suggest that the therapeutic success of combined FAK and MDM2 inhibition in mesothelioma depends on the precise matching of MDM2 inhibitors with the TP53 genotypes, and highlight the need for genotype-based selection of MDM2 inhibitors.

SMJN in current practice remains predominantly metastatic adenocarcinoma, most often gastrointestinal or gynecologic in origin. However, rare entities-including mesothelioma, melanoma, and lymphoma-underscore the need for a broad diagnostic differential. Fine-needle aspiration offers a rapid, minimally invasive diagnostic bridge and reinforces that the umbilicus remains a valuable clinical marker of an often occult malignancy.

P1, N=24, Not yet recruiting, Weijia Fang, MD

Conversely, KAP1 expression was significantly negatively correlated with MTAP and MSLN. GSEA reveals KAP1-associated enrichment of DNA repair, cell cycle, and proteostasis pathways in TCGA-MESO.ConclusionKAP1 is highly expressed in PM and functions as an oncogene-like regulator, enhancing tumor cell growth and aggressiveness.Clinical trial registration2023-28.