Tumor treating fields in malignant pleural mesothelioma: from cytoskeletal collapse to immunophenotypic conversion
TTFields physically disrupt actin‑dependent intercellular “tunneling nanotubes,” thereby severing the tumor’s communication and metabolic rescue networks.
The therapeutic efficacy in malignant pleural mesothelioma (MPM) is severely hindered by its dense stromal barrier and immunosuppressive microenvironment. Although Tumor Treating Fields (TTFields) have demonstrated significant survival benefits in clinical trials, their underlying mechanisms extend well beyond simple mitotic arrest. This review delineates a “multidimensional biophysical remodeling” atlas of TTFields in MPM. First, we highlight that TTFields physically disrupt actin‑dependent intercellular “tunneling nanotubes,” thereby severing the tumor’s communication and metabolic rescue networks. Second, physical stress downregulates the Fanconi Anemia‑BRCA pathway, inducing a state of “conditional BRCAness” that specifically sensitizes tumors to DNA‑damaging agents. 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.
Severing tunneling nanotubes (TNTs) undermines the tumor’s ability to share organelles and metabolic resources between cells, thereby sensitizing the tumor to chemotherapy and reducing the likelihood of drug‑resistant clones emerging.
Evidence level: Feltételezés / hírjelzés. Nincs önálló tudományos bizonyíték.
Related signals
- Moving Beyond Morphology: Toward a Morpho‑Molecular Classification of Pleural Mesothelioma
- Comparison of Survival by Multimodal Treatment Regimen Among Malignant Pleural Mesothelioma Patients in an Integrated Health System
- Systemic Treatments for Unresectable Pleural Mesothelioma: A Review of the Literature
- Prognostic impact of somatic mutations among patients with pleural and peritoneal mesothelioma
- Tumor Treating Fields (TTFields) for Pleural Mesothelioma