Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy

• Published in: Cell reports. Medicine Vol. 5; no. 7; p. 101626
• Main Authors: Mpekris, Fotios, Panagi, Myrofora, Charalambous, Antonia, Voutouri, Chrysovalantis, Stylianopoulos, Triantafyllos
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 16.07.2024; Elsevier
• Subjects: Angiogenesis Inhibitors - therapeutic use; Animals; anti-angiogenic therapy; biomarkers; engineered bacteria; Humans; Immunotherapy - methods; Neoplasms - immunology; Neoplasms - pathology; Neoplasms - therapy; Neovascularization, Pathologic - pathology; precision oncology; Review; Tumor Microenvironment - drug effects; tumor normalization; precision oncology; anti-angiogenic therapy; engineered bacteria; tumor normalization; biomarkers
• ISSN: 2666-3791; 2666-3791
• DOI: 10.1016/j.xcrm.2024.101626

Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including increased tumor stiffness and accumulation of intratumoral forces, can determine the success of cancer treatments, defining the tumor’s “mechanopathology” profile. These abnormalities cause extensive vascular compression, leading to hypoperfusion and hypoxia. Hypoperfusion hinders drug delivery, while hypoxia creates an unfavorable TME, promoting tumor progression through immunosuppression, heightened metastatic potential, drug resistance, and chaotic angiogenesis. Strategies targeting TME mechanopathology, such as vascular and stroma normalization, hold promise in enhancing cancer therapies with some already advancing to the clinic. Normalization can be achieved using anti-angiogenic agents, mechanotherapeutics, immune checkpoint inhibitors, engineered bacterial therapeutics, metronomic nanomedicine, and ultrasound sonopermeation. Here, we review the methods developed to rectify tumor mechanopathology, which have even led to cures in preclinical models, and discuss their bench-to-bedside translation, including the derivation of biomarkers from tumor mechanopathology for personalized therapy. [Display omitted] Solid tumor pathology, characterized by abnormalities in the tumor microenvironment, impairs efficacy of therapy. Mechanical factors shape the tumor’s “mechanopathology” profile and influence treatment success. Mpekris et al. review methods to rectify tumor mechanopathology, achieving preclinical cures, and discuss their clinical translation, including biomarker development for personalized therapy.