How Do Antineoplastic Angiogenesis Inhibitors Work?

Angiogenesis inhibitors, also called anti-angiogenics, are drugs that block angiogenesis and are an important part of treatment for some types of cancer. 

Angiogenesis is the formation of new blood vessels which are controlled by chemical signals in the body. Normally, the angiogenesis stimulating, and inhibiting effects of these chemical signals are balanced so that blood vessels form only when and where they are needed, such as during growth and healing. 

Angiogenesis plays a critical role in the growth of cancer because solid tumors need a blood supply to grow beyond a few millimeters in size. Tumor cells can stimulate nearby normal cells to produce angiogenesis signaling molecules such as pro-angiogenic factors including angiogenin, vascular endothelial growth factor, fibroblast growth factor, and transforming growth factor-β. The resulting new blood vessels “feed” growing tumors with oxygen and nutrients, allowing the tumor to enlarge and the cancer cells to invade nearby tissue, to move throughout the body, and to form new colonies of cancer cells called metastases.

Angiogenesis inhibitors are unique cancer-fighting agents because they block the growth of blood vessels that support tumor growth rather than blocking the growth of tumor cells themselves. These drugs prevent or slow down the growth of cancer by starving it of its needed blood supply.

Angiogenesis inhibitors are administered orally once daily with or without food.

Angiogenesis inhibitors work in the following ways:

• They inhibit the growth of new blood vessels (angiogenesis).
• They belong to a class known as “immunomodulatory agents” that work by helping the bone marrow to produce normal blood cells and by killing abnormal cells in the bone marrow.
• They belong to a class called “kinase inhibitors” that work by blocking the action of an abnormal protein that signals cancer cells to multiply. This helps to slow down or stop the spread of cancer cells.
• They exert direct cytotoxicity by increasing apoptosis (death of cells that occurs as a normal and controlled part of an organism's growth or development) and inhibit the proliferation of hematopoietic malignant cells.
• In addition, they inhibit the production of pro-inflammatory cytokines, which are implicated in various hematologic malignancies.

Angiogenesis inhibitors are used to treat conditions such as:

• Myelodysplastic syndromes (a group of conditions that can occur when the blood-forming cells in the bone marrow become abnormal)
• Multiple myeloma (a type of cancer of the bone marrow)
• Mantle cell lymphoma (fast-growing cancer that begins in the cells of the immune system)
• Follicular lymphoma or marginal zone lymphoma (cancer that affects white blood cells called lymphocytes)
• Kaposi sarcoma (a type of cancer that forms in the lining of blood and lymph vessels)
• Colorectal cancer (cancer that begins in the large intestine)
• Gastrointestinal stromal tumors (a type of tumor that grows in the stomach, intestine [bowel], or esophagus [a tube that connects the throat with the stomach])
• Hepatocellular carcinoma (a type of liver cancer)
• Erythema nodosum leprosum (episodes of skin sores, fever, and nerve damage that occur in people with leprosy)

Some of the common side effects include:

• Nausea
• Vomiting
• Diarrhea
• Abdominal pain
• Loss of appetite
• Dry skin/mouth
• Constipation
• Weakness
• Headache
• Weight loss
• Fever
• Fatigue 

Other rare side effects include:

• Hypertension (high blood pressure)
• Hypocalcemia (low blood calcium level)
• Drowsiness (abnormally sleepy during the day)
• Shortness of breath
• Fast, slow, or pounding heartbeat
• Dizziness (feeling faint, weak, or unsteady)
• Trouble sleeping
• Numbness/tingling of arms/legs
• Depression
• Blistering, peeling, or shedding skin
• Yellowing of the skin or eyes
• Dark-colored urine
• Hoarseness of voice
• Tremor (an involuntary, rhythmic muscle contraction, leading to shaking movements in one or more parts of the body)
• Thrombocytopenia (low blood platelet count)
• Increased aspartate transaminase/alanine transaminase

Information contained herein is not intended to cover all possible side effects, precautions, warnings, drug interactions, allergic reactions, or adverse effects. Check with your doctor or pharmacist to make sure these drugs do not cause any harm when you take them along with other medicines. Never stop taking your medication and never change your dose or frequency without consulting your doctor.

Generic and brand names of antineoplastic angiogenesis inhibitors include:

• Lenalidomide
• Pomalidomide
• Pomalyst
• Regorafenib
• Revlimid
• Stivarga
• Thalidomide
• Thalomid