ANTI-ANGIOGENESIS DRUG OVERVIEW

The formation of new blood vessels in the body is called angiogenesis. While angiogenesis is a natural process essential to wound healing, unfortunately it also feeds the growth of cancerous tumors. A newly formed cancerous tumor cannot grow beyond a certain size without the aid of blood vessels. Tumors signal nearby blood vessels by secreting Vascular Endothelial Growth Factors (VEGF). This induces blood vessel growth into the tumor, providing a flow of oxygen and essential nutrients necessary for malignancy.

VEGF is a family of naturally occurring proteins that stimulate growth and survival of the cells of the vascular system, the network of blood vessels (arteries arterioles, venules, capillaries and veins) in the body. VEGF is found in very high levels in most malignant mesothelioma patients; this helps the tumor to grow and spread rapidly. Angiogenesis inhibitors prevent the continuous formation of new blood vessels by halting production of VEGF. They can either occur naturally or be produced synthetically (as anti-angiogenesis drugs).

Anti-Angiogenesis Drugs

Anti-angiogenesis drugs are relatively new. Those that have been used in animal studies have been successful in shrinking and killing cancerous cells. Although anti-angiogenesis drugs are yet to prove as successful in human studies, they are expected to yield similar results.

Three anti-angiogenesis drugs receiving a great deal of attention are Veglin, Avastin and PXD101.. Veglin is designed to target a wide range of cancers, including malignant mesothelioma and renal cell carcinoma, while Avastin is designed primarily to target cancers of the colon and rectum. PXD101 is a new anti-angiogenesis drug that is in a Phase I clinical trial at the Yale Cancer Medical Center.

Avastin

Manufactured by Genentech Inc., Avastin (bevacizumab) is an anti-angiogenesis drug that has been approved by the Food and Drug Administration (FDA) to treat metastatic colorectal cancer. Avastin is used in combination with other forms of treatment such as chemotherapy. In a clinical trial, a handful of patients diagnosed with metastatic colorectal cancer were given Avastin in addition to chemotherapy, while the rest of the group was given only chemotherapy. The study found that the tumors of patients who took Avastin in addition to chemotherapy shrank in size and were kept from growing more often than in patients who received only chemotherapy. Those who took Avastin in conjunction with chemotherapy lived longer than patients who received only chemotherapy.

PXD101

PXD101 is an orally administered histone deacetylase inhibitor that is being used as a second line therapy in treating patients with mesothelioma that cannot be removed with surgery. It is an anti-angiogenesis drug treatment that is being used in clinical trials across the United Stated including the Yale Cancer Medical Center. Heading the research into this drug at Yale is Dr. Scott Gettinger, a medical oncologist in the Thoracic Oncology Program (TOP) at Yale who has gotten PXD101 into Phase 1 of FDA clinical trials. Although not the same for every patient the most common side effects of PXD101 include being tired and/or fatigued, along with low-grade nausea, which can be treated with medications. These side effects have proven to be minimal and less severe than the effects of chemotherapy or radiation.

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