Introduction:
The formation of small blood vessels to transfer oxygen-rich blood and nutrients to different tissue is called angiogenesis. Cancer is the uncontrolled growth of cells. Sufficient nutrients and oxygen-rich blood are needed for tumor cell growth. The growth of the tumor can be reduced by blocking the supply of nutrients and oxygen for the tumor cells. This is blocked by using the angiostatic approach with the help of angiogenesis inhibitors. Thus cancer can be treated.
What Is Angiogenesis?
New blood vessels or capillary formation from preexisting blood vessels is called angiogenesis. It normally helps supply nutrients and oxygen-rich blood to the organs and different parts of the body. They also help in wound healing. Tiny blood vessels called capillaries supply oxygen-rich blood to different tissues and organs. If some tissues have hypoxia or do not receive enough oxygen, the cells send chemical signals causing angiogenesis in the endothelial cells or the cells lining the blood vessels. Angiogenesis or blood vessels can be formed in two types- sprouting or new growth of blood vessels from the endothelial cells by receiving chemical signals like vascular endothelial growth factor or VEGF. The next type is splitting the blood vessel to form a new capillary.
What Is the Role of Angiogenesis in Tumor Metastasis?
Angiogenesis helps tumor growth and metastasis by supplying tumor cells with nutrients and oxygen. Like normal cells, the tumor cells can also send chemical signals when they do not receive nutrients and oxygen. Thus angiogenesis occurs to supply oxygen-rich blood and nutrients to supply the tumor cells and helps in the growth of the tumor.
What Are Angiogenesis Regulators?
Angiogenesis is a multistep process. Initially, there will be degradation of the basement membrane by protease enzyme. The endothelial cells will migrate and start to sprout or grow, then there will be endothelial cell proliferation, and there will be the formation of a lumen to help in the flow of the blood. These are regulated by angiogenesis-enhancing and inhibiting factors.
What Are Angiogenesis Enhancing Factors?
Angiogenesis-enhancing factors are the chemicals that help to form new blood vessels to supply oxygen-rich blood and nutrients. They are also called positive regulators.
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Vascular Endothelial Growth Factor (VEGF) - Helps in the growth of new blood vessels by sending signals. It is produced by both normal cells and tumor cells. It is also called vascular permeability factor or VPF.
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Fibroblast Growth Factor (FGF) - They are cell signaling molecules usually produced by macrophages. They are seen in tumor cells also.
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Matrix Metalloproteinase (MMPs) - Helps in tissue remodeling in morphogenesis, angiogenesis, or metastasis.
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Integrins - They are transmembrane receptors that help in adhesion.
What Are Angiogenesis Inhibitors?
Angiogenesis inhibitors help to block the blood and nutrient supply to the tumor cells to prevent the growth and spread of the tumor. Angiogenesis inhibitors can be exogenous or endogenous.
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Endogenous Inhibitors - They are found inside the body and are involved in the daily process of forming blood vessels. They are formed from the basement membrane. These endogenous inhibitors interfere with the proliferation of endothelial cells and migration. They can be matrix-derived and non-matrix-derived. Some endogenous inhibitors are angiostatin, endostatin, thrombospondin, angiopoietins, etc.
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Exogenous Inhibitors - They are from outside the body. They inhibit the growth and migration of endothelial cells. Drugs are given to inhibit angiogenesis. Bevacizumab, Vitaxin, and Marimastat are some exogenous inhibitors targeted to a specific site. Angiogenesis inhibitors are also present in some common diets.
What Is Angiostatic Approach in Cancer Treatment?
The angiostatic approach can treat both primary and metastatized tumor growth. The angiostatic approach is made by inhibiting angiogenesis. Angiogenesis inhibitors are given orally or intravenously. Vaccination for treating cancer by angiostatic approach by targeting the endothelial cell of the tumor directly is available. A study shows DNA (deoxyribonucleic acid) vaccine can also inhibit cancer growth. Specific markers in the endothelial lining of the tumor should be identified to target the angiogenesis inhibitor at the tumor site. When combined with additional therapies, angiogenetic inhibitors are very effective in treating cancer. Angiogenesis inhibitors can be used with chemotherapy, radiation therapy, or immunotherapy.
Which Are the Angiogenesis Inhibitors That Are Used to Treat Cancer?
Some of the angiogenesis inhibitors that are used to treat cancer are -
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Axitinib is used to treat kidney cancer.
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Bevacizumab treats glioblastoma, cervical, kidney, liver, colorectal, lung, and ovarian cancers.
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Cabozantinib is used to treat kidney cancer, liver cancer, and thyroid cancer.
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Everolimus is used to treat breast cancer, kidney cancer, and neuroendocrine cancers of the lung, pancreas, and gastrointestinal tract.
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Lenalidomide treats follicular lymphoma, marginal zone lymphoma, multiple myeloma, and anemia caused by myelodysplastic syndromes.
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Lenvatinib treats endometrial carcinoma, liver, kidney, and thyroid cancers.
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Pazopanib hydrochloride is used to treat soft tissue sarcoma and kidney cancer.
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Ramucirumab treats colorectal cancer, adenocarcinoma of the stomach, liver cancer, and adenocarcinoma present in the gastroesophageal junction.
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Regorafenib is used to treat liver cancer, colorectal cancer, and gastrointestinal stomach tumor.
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Sorafenib is used to treat kidney cancer, thyroid cancer, and liver cancer.
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Sunitinib treats kidney cancer, gastrointestinal stromal tumor, and pancreatic neuroendocrine tumors.
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Thalidomide is used to treat multiple myeloma. Thalidomide is contraindicated in pregnant women because it can cause birth defects.
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Vandetanib is used to treat medullary thyroid cancer.
What Are the Side Effects of Angiogenesis Inhibitors?
Angiogenesis inhibitors can cause many side effects because angiogenesis helps in the supply of nutrients and blood with oxygen to normal tissue also. By using inhibitors, they block the blood supply to the normal tissues also. Some of the side effects are mentioned below-
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Increased blood pressure.
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Hand-foot syndrome (swelling on the arms, feet, and fingertips, which are painful).
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Dryness or itching on the skin.
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Fatigue and weakness.
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Diarrhea.
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Blood clots or bleeding.
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Stroke.
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Delayed wound healing.
Conclusion:
Angiogenesis helps in tumor growth, both primary and metastatic tumors. When the balance between angiogenesis enhancing and inhibiting factors change, angiogenesis can occur in tumor cells. To prevent tumor growth, angiogenesis inhibitors are used. Angiogenesis inhibitors targeting specific sites are used to avoid any adverse effects that can cause to normal tissues and organs. Beverages like red wine and green tea contain angiogenesis inhibitors.
