Vascular Normalization: A New Window Opened for Cancer Therapies
Ting Yang1, Hongqi Xiao2, Xiaoxia Liu1
1Department of General Surgery, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, China.
Abstract:
Preclinical and clinical antiangiogenic approaches, with multiple side effects such as resistance, have not been proved to be very successful in treating tumor blood vessels which are important targets for tumor therapy. Meanwhile, restoring aberrant tumor blood vessels, known as tumor vascular normalization, has been shown not only capable of reducing tumor invasion and metastasis but also of enhancing the effectiveness of chemotherapy, radiation therapy, and immunotherapy. In addition to the introduction of such methods of promoting tumor vascular normalization such as maintaining the balance between proangiogenic and antiangiogenic factors and targeting endothelial cell metabolism, microRNAs, and the extracellular matrix, the latest molecular mechanisms and the potential connections between them were primarily explored. In particular, the immunotherapy-induced normalization of blood vessels further promotes infiltration of immune effector cells, which in turn improves immunotherapy, thus forming an enhanced loop. Thus, immunotherapy in combination with antiangiogenic agents is recommended. Finally, we introduce the imaging technologies and serum markers, which can be used to determine the window for tumor vascular normalization.
Insights
Tumor vascular normalization, not antiangiogenic therapy, improves cancer treatment. This approach enhances chemotherapy, radiation, and immunotherapy effectiveness by restoring blood vessels and promoting immune cell infiltration.
Area of Science:
- Oncology
- Vascular Biology
- Immunotherapy
Background:
- Antiangiogenic therapies for tumor blood vessels show limited success due to side effects like resistance.
- Aberrant tumor vasculature hinders effective cancer treatment and promotes metastasis.
- Tumor vascular normalization offers a promising strategy to improve therapeutic outcomes.
Purpose of the Study:
- To explore molecular mechanisms underlying tumor vascular normalization.
- To investigate the interplay between vascular normalization and immunotherapy.
- To identify biomarkers and imaging technologies for optimizing vascular normalization strategies.
Main Methods:
- Review of preclinical and clinical studies on antiangiogenic and vascular normalizing approaches.
- Exploration of molecular targets including endothelial cell metabolism, microRNAs, and extracellular matrix.
- Analysis of the synergistic effects of immunotherapy and vascular normalization.
Main Results:
- Tumor vascular normalization reduces invasion and metastasis.
- Normalization enhances the efficacy of chemotherapy, radiation, and immunotherapy.
- Immunotherapy-induced vascular normalization boosts immune effector cell infiltration, creating a positive feedback loop.
- Imaging technologies and serum markers can identify optimal windows for vascular normalization therapy.
Conclusions:
- Tumor vascular normalization is a superior strategy compared to traditional antiangiogenic approaches.
- Combining immunotherapy with agents promoting vascular normalization is recommended for enhanced therapeutic benefits.
- Biomarkers and imaging are crucial for timing and monitoring vascular normalization interventions.
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