Regulating Vascular Normalization for Improved Radiotherapy Sensitization
Introduction
Conventional drug therapies have been the cornerstone of cancer treatment for many years. However, in recent times, physical strategies have become increasingly popular in regulating vascular normalization. These include the use of laser, electricity, ultrasound, and magnetic field, among others. Physical strategies have been found to be effective in regulating vascular normalization and are mostly used in chemotherapy. While the related application of sensitization by radiotherapy needs more exploration, there is a growing body of research that suggests that normalization of blood vessels improves the efficacy of radiotherapy.
Radiotherapy and Vascular Normalization
Radiotherapy primarily causes apoptosis through direct or indirect damage to DNA via ionizing radiation, leading to DNA strand breaks. In tumors, the efficacy of radiotherapy is attenuated by the malignant tumor microenvironment (TME), such as hypoxia. The tumor vasculature, due to the imbalance of various angiogenic and anti-angiogenic factors, leads to irregular morphology of tumor neovasculature, disordered arrangement of endothelial cells, and too little peripheral coverage. This ultimately leads to a TME characterized by hypoxia, low pH, and high interstitial pressure. This deleterious TME further exacerbates the adverse effects of tumor neovascularization and weakens the efficacy of conventional radiotherapy.
The Role of Vascular Normalization
Normalization of blood vessels can improve tumor microenvironment and thus the efficacy of radiotherapy. By modulating vascular normalization, it is possible to minimize the adverse effects of tumor neovascularization and enhance the effectiveness of radiotherapy. This is because normalization of blood vessels helps to restore the balance of various angiogenic and anti-angiogenic factors, leading to the formation of regular tumor vasculature, and optimal perfusion. It also helps to reduce interstitial fluid pressure effectively. This creates an environment that promotes oxygen and nutrient delivery to the tumor, making radiotherapy more effective.
Strategies for Vascular Normalization
Several strategies have been proposed for regulating vascular normalization to improve radiotherapy sensitization:
Cancer Immunotherapy
Cancer immunotherapy enhances the immune system’s ability to identify and kill cancer cells. It has been found to be effective in promoting vascular normalization and the efficacy of radiotherapy sensitization. Immunotherapeutic agents, such as anti-VEGF antibody, promote vascular normalization by reducing the permeability of tumor blood vessels. This, in turn, helps to reduce the tumor’s interstitial fluid pressure and enhances oxygen and nutrient delivery to the tumor. As a result, the efficacy of radiotherapy is improved.
Chemotherapy
Chemotherapy drugs, such as docetaxel, have been found to be effective in promoting vascular normalization. By inducing tumor cell apoptosis, chemotherapy drugs reduce the number of cancer cells in the tumor. This, in turn, reduces the production of proangiogenic factors and promotes vascular normalization. Through normalization of blood vessels, chemotherapy drugs help to improve oxygen and nutrient availability to the tumor, and thus enhance the efficacy of radiotherapy sensitization.
Nitric Oxide Synthase (NOS) Inhibitors
NOS inhibitors are effective in promoting vascular normalization and the efficacy of radiotherapy sensitization. By inhibiting the production of nitric oxide, NOS inhibitors reduce the permeability of tumor blood vessels and thus enhance vascular normalization. This results in a reduction of interstitial fluid pressure, leading to improved oxygen and nutrient delivery to the tumor, thus enhancing the effectiveness of radiotherapy.
Combination Therapy
The combination of vascular normalization agents and radiotherapy has been found to be effective in improving radiotherapy sensitization. The use of vascular normalization agents such as bevacizumab, and radiotherapy increases the normalization of blood vessels, reduces interstitial fluid pressure, and enhances oxygen and nutrient delivery to the tumor. This, in turn, leads to an improved response to radiotherapy.
Conclusion
Regulating vascular normalization is an effective strategy to improve radiotherapy sensitization. The use of alternative medicines such as cancer immunotherapy, chemotherapy, and NOS inhibitors can help to promote vascular normalization and enhance the efficacy of radiotherapy. Furthermore, combination therapy with vascular normalization agents and radiotherapy has been found to be an effective approach to promote vascular normalization. Further research is needed to examine the full potential of these strategies to improve radiotherapy sensitization.
Originally Post From https://www.sciencedirect.com/science/article/pii/S2405844024086298
