Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy

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 “mech...

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Published inCell reports. Medicine Vol. 5; no. 7; p. 101626
Main Authors Mpekris, Fotios, Panagi, Myrofora, Charalambous, Antonia, Voutouri, Chrysovalantis, Stylianopoulos, Triantafyllos
Format Journal Article
LanguageEnglish
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
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Abstract 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.
AbstractList 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.
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.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.
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.
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. 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.
ArticleNumber 101626
Author Charalambous, Antonia
Stylianopoulos, Triantafyllos
Voutouri, Chrysovalantis
Panagi, Myrofora
Mpekris, Fotios
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  surname: Mpekris
  fullname: Mpekris, Fotios
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  givenname: Myrofora
  surname: Panagi
  fullname: Panagi, Myrofora
  organization: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus
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  givenname: Antonia
  surname: Charalambous
  fullname: Charalambous, Antonia
  organization: Cancer Biophysics Laboratory, Department of Mechanical and Manufacturing Engineering, University of Cyprus, Nicosia, Cyprus
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  givenname: Chrysovalantis
  surname: Voutouri
  fullname: Voutouri, Chrysovalantis
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  email: tstylian@ucy.ac.cy
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Keywords precision oncology
anti-angiogenic therapy
engineered bacteria
tumor normalization
biomarkers
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Snippet Solid tumor pathology, characterized by abnormalities in the tumor microenvironment (TME), challenges therapeutic effectiveness. Mechanical factors, including...
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SubjectTerms 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
Title Modulating cancer mechanopathology to restore vascular function and enhance immunotherapy
URI https://dx.doi.org/10.1016/j.xcrm.2024.101626
https://www.ncbi.nlm.nih.gov/pubmed/38944037
https://www.proquest.com/docview/3073712354
https://pubmed.ncbi.nlm.nih.gov/PMC11293360
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