Normalizing Function of Tumor Vessels: Progress, Opportunities, and Challenges

Area of Science:

• Oncology
• Tumor Microenvironment
• Vascular Biology

Background:

• Abnormal tumor vasculature leads to hypoxia, low pH, and high pressure, promoting tumor progression and treatment resistance.
• The tumor microenvironment's abnormalities hinder effective delivery and function of anticancer therapies.
• Desmoplasia can further impair vascular function by physically compressing blood vessels within the tumor.

Purpose of the Study:

• To review the progress and application of the vessel normalization concept in cancer therapy.
• To explore strategies for normalizing tumor vasculature and the extracellular matrix to improve treatment outcomes.
• To identify future opportunities and challenges in utilizing normalization approaches for cancer patients.

Main Methods:

• Review of preclinical and clinical evidence supporting the vessel normalization hypothesis.
• Investigation of molecular mechanisms underlying vessel normalization.
• Assessment of strategies targeting extracellular matrix normalization.

Main Results:

• Antiangiogenesis agents can transiently normalize tumor vessels, creating a therapeutic window for enhanced drug efficacy.
• Normalization of the extracellular matrix improves vascular function and treatment outcomes.
• Evidence supports the efficacy of normalization strategies in both preclinical models and clinical settings.

Conclusions:

• The normalization concept offers a promising strategy to overcome treatment resistance in cancer.
• Combining vessel and extracellular matrix normalization holds potential for improving patient outcomes.
• Further research and clinical application of normalization strategies are warranted to optimize cancer therapy.