Inhibiting Angiogenesis to Treat Cancer

What Is Angiogenesis?

Angiogenesis is defined as the process of forming new blood vessels from pre-existing vasculature formed in the early stage of vasculogenesis (the process of blood vessel formation in the embryo). It occurs throughout life, beginning in utero and continuing till old age. It plays a vital role in growth, development, and wound healing. The two types of angiogenesis include;

1. Sprouting Angiogenesis: In sprouting angiogenesis, new blood vessels sprout or bud from the pre-existing vessels.

2. Intussusceptive Angiogenesis: It is also called splitting angiogenesis. In intussusceptive angiogenesis, new blood vessels are formed by splitting the pre-existing blood vessel into two.

Angiogenesis is stimulated by various growth factors called angiogenic growth factors. The different angiogenic growth factors that stimulate angiogenesis include

• Basic fibroblast growth factor (bFGF).

• Granulocyte colony-stimulating growth factor (G-CSF).

• Vascular endothelial growth factor (VEGF).

• Transforming growth factor-alpha and beta.

• Platelet-derived growth factor (PDGF).

• Interleukin-8 (IL-8).

Vascular endothelial growth factors secreted by tumor cells stimulate blood vessel growth and allow for tumor growth and expansion.

What Is the Role of Angiogenesis in Cancer?

The tumor requires blood supply to grow beyond a few millimeters in size. In general, tumor cells lack blood supply, due to which the growth of the tumor is blocked up to a specific time. However, at times the tumor may start secreting angiogenic growth factors that stimulate the formation of new blood vessels from pre-existing blood vessels. As a result, the newly formed blood vessels feed the tumor with oxygen and nutrients allowing the tumor to enlarge and leading cancer cells to invade the nearby tissue. Therefore inhibiting angiogenesis is necessary for controlling tumor growth. A specific type of drug named angiogenesis inhibitors are used to inhibit angiogenesis.

What Are Angiogenesis Inhibitors and How Do They Work?

• Drugs that inhibit angiogenesis are referred to as angiogenesis inhibitors. It is also called an anti-angiogenic drug. The main goal of angiogenesis inhibitors in cancer treatment is to prevent new blood vessel formation that stimulates tumor growth rather than blocking the growth of tumor cells.

• Angiogenesis inhibitors inhibit new blood vessel growth in different ways. Some angiogenesis inhibitors are monoclonal antibodies that specifically bind to vascular endothelial growth factor (VEGF) and target it. The vascular endothelial growth factor cannot activate its receptors when the angiogenesis inhibitors bind to it.

• The other mechanism by which angiogenesis inhibitors work is blocking the angiogenesis growth factor signaling pathway that stimulates tumor growth. Some angiogenesis inhibitors act as immunomodulatory agents that prevent tumor growth by stimulating or suppressing the immune system.

• Angiogenesis inhibitors prevent tumor growth by inhibiting angiogenesis rather than blocking cancer cell growth. Therefore combining angiogenesis inhibitors with other cancer treatments is found to be more effective in treating certain types of cancer.

What Are the Different Angiogenesis Inhibitors Used in Cancer Treatment?

Angiogenesis inhibitors can be given either alone or in combination with other cancer treatments. Several angiogenesis inhibitors are approved by the FDA (Food and Drug Administration) for treating different types of cancers. The angiogenesis inhibitors approved by FDA include;

1. Bevacizumab: Bevacizumab is used for treating cervical, colorectal, kidney, liver, and non-small cell lung cancers. It can also treat ovarian, peritoneal, and fallopian tube cancers.

2. Axitinib: It is used to treat kidney cancer.

3. Cabozantinib: It is used for the treatment of;

• Kidney cancer.

• Liver cancer.

• Differentiated thyroid cancer.

• Medullary thyroid cancer.

4. Everolimus: Is used for the treatment of;

• Breast cancer.

• Kidney cancer.

• Neuroendocrine lung cancer.

• Gastrointestinal neuroendocrine tumors.

• Pancreatic neuroendocrine tumors (PNET).

• Subependymal giant cell astrocytoma (a type of noncancerous brain tumor).

5. Lenvatinib: Is proven to be beneficial in the treatment of;

• Liver cancer.

• Thyroid cancer.

• Kidney cancer.

• Endometrial carcinoma.

6. Lenalidomide: Is used for the treatment of;

• Follicular lymphoma - Follicular lymphoma is a very slow-growing cancer that appears in the lymph nodes of the bone marrow and other organs.

• Mantle cell lymphoma - Mantle cell lymphoma is a rare blood cancer that occurs in the white blood cells in the lymph nodes.

• Marginal zone lymphoma -This is a type of Non-Hodgkin’s lymphoma that can transform into a more aggressive lymphoma (cancer).

• Multiple myeloma - This is a condition in which plasma cells become cancerous.

7. Ramucirumab: It is approved to treat;

• Liver cancer.

• Non-small cell lung cancer.

• Stomach adenocarcinoma.

8. Regorafenib: It is used for the treatment of;

• Colorectal cancer.

• Liver cancer.

• Gastrointestinal stromal tumor.

9. Thalidomide: It is used for the treatment of multiple myeloma. It is not recommended for pregnant ladies because it may lead to severe birth defects.

10. Vandetanib: It is authorized for the treatment of medullary thyroid cancer.

11. Pazopanib Hydrochloride: It is employed in treating kidney cancer and soft tissue sarcoma.

12. Ziv-aflibercept: It is used for the treatment of colorectal cancer.

How Are Angiogenesis Inhibitors Given in Patients?

The doctor can prescribe angiogenesis inhibitors in the form of oral pills or be given intravenously (IV). Before taking angiogenesis inhibitors, the patients are advised to discuss the side effects associated with the drug. In addition, the patients should take the medicines at regular intervals as prescribed by the doctor to avoid missing a dose. If a dose is missed, then the patient should inform the doctor.

What Are the Side Effects of Angiogenesis Inhibitors?

Angiogenesis plays a vital role in normal growth and development and wound healing. Therefore inhibiting angiogenesis can cause a wide range of side effects. The most common symptoms of angiogenesis inhibitors include;

• Fatigue.

• Diarrhea.

• Delayed wound healing.

• Skin rashes.

• Dry and itchy skin.

• Low blood cell counts.

• High blood pressure.

• Hand-foot syndrome (a syndrome that causes numbness, tingling, swelling, and burning sensations in hands and feet).

If angiogenesis inhibitors cause any side effects in patients, then they should inform the healthcare provider. The healthcare provider will help manage the symptoms by prescribing some medicines.

What Are Anti-Angiogenic Foods?

Our diet can play a significant role in cancer prevention and control. Some foods that we eat in our daily life can help us fight against cancer. One such food that helps prevent tumor growth is anti-angiogenic foods. Anti-angiogenic foods are mainly plant-based foods with some naturally occurring anti-angiogenic substances that help prevent angiogenesis. The most common examples of anti-angiogenic foods are;

• Green tea.

• Different types of berries, such as blackberries, raspberries, and gooseberries.

• Red wine.

• Dark chocolate.

• Fruits like watermelon, citrus fruits, and avocados.

• Green leafy vegetables.

Conclusion:

Tumor growth is stimulated by angiogenesis; inhibiting angiogenesis can help block tumor growth and recurrence. Angiogenesis inhibitors help inhibit angiogenesis in cancer. FDA has approved various angiogenesis inhibitors for cancer treatments. Angiogenesis inhibitors treat cancer only by blocking tumor growth rather than tumor cell growth; therefore, combining angiogenesis inhibitors with other cancer treatments is more effective.