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Antiangiogenic therapy: Markers of response, "normalization" and resistance
Karima El Alaoui-Lasmaili1, Béatrice Faivre2
1Université de Lorraine, CNRS, CRAN, F-54000 Nancy, France.
Abstract:
Currently in cancer treatment, one premise is to use antiangiogenic therapies in association with chemotherapy or radiotherapy to augment their efficacy by benefiting from the vascular "normalization" induced by antiangiogenic therapy. This concept defines the time during which the tumor blood vessels adopt normal-like morphology and functionality, i.e. the blood vessels become more mature, the perfusion augments and hypoxia decreases. To date, there is such a diversity of treatment protocols where the type of antiangiogenic to adopt, its dose and duration of administration are different, that knowing when and how to treat is problematic. In this review, we analyzed thoroughly preclinical and clinical studies that use antiangiogenic treatments to benefit from the "normalization" and showed that the effects depend on the type of antiangiogenic administrated (anti-VEGF, anti-VEGFR, Multi-Kinase Inhibitor) and on the duration of treatment. Finally, biomarkers of "normalization" and resistance that could be used in the clinic are presented.
Insights
Antiangiogenic therapy normalizes tumor vasculature, enhancing cancer treatments. Optimal timing and drug choice are crucial, as effects vary by agent and duration, with biomarkers aiding clinical decisions.
Area of Science:
- Oncology
- Vascular Biology
- Cancer Therapeutics
Background:
- Antiangiogenic therapies are combined with chemotherapy or radiotherapy to improve cancer treatment efficacy.
- Vascular normalization, characterized by mature blood vessels, increased perfusion, and reduced hypoxia, is the proposed mechanism of action.
Purpose of the Study:
- To analyze preclinical and clinical studies on antiangiogenic therapy-induced vascular normalization in cancer treatment.
- To clarify the impact of different antiangiogenic agents and treatment durations on vascular normalization.
- To identify potential biomarkers for predicting normalization and resistance.
Main Methods:
- Comprehensive review of preclinical and clinical studies involving antiangiogenic treatments.
- Analysis of treatment protocols, including antiangiogenic agent type, dosage, and administration duration.
- Evaluation of reported outcomes related to vascular normalization and treatment efficacy.
Main Results:
- The efficacy of vascular normalization is dependent on the specific antiangiogenic agent used (e.g., anti-VEGF, anti-VEGFR, Multi-Kinase Inhibitor).
- Treatment duration significantly influences the extent and effectiveness of vascular normalization.
- Biomarkers for both vascular normalization and treatment resistance were identified.
Conclusions:
- The timing and choice of antiangiogenic therapy are critical for achieving beneficial vascular normalization in cancer treatment.
- Understanding the differential effects of various antiangiogenic agents and treatment durations is essential for optimizing therapeutic strategies.
- Identified biomarkers hold potential for guiding clinical decisions and personalizing cancer therapy.