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Angiogenesis & Tumor Growth

All tissues, including tumors, require oxygen and nutrients for growth and survival. Tissues create and replace blood vessels as necessary, but the process is regulated by a complex cascade of enzymes and chemical signals. A distinguishing feature of cancer cells is their ability to override normal controls limiting angiogenesis, or blood vessel production. With no restrictions on its ability to supply itself with nutrients, the tumor grows and metastasizes.

  1. What Is Angiogenesis

    • Angiogenesis is the formation of new blood vessels. Blood vessels carry nutrients and oxygen to the tissues while removing carbon dioxide and metabolic wastes. Angiogenesis is coordinated with tissue growth and is regulated by a series of growth factors made up of proteins and enzymes.

    Angiogenesis and Tumor Growth

    • Tumors must create an independent blood supply to feed the uncontrolled growth and metastasis of the cancer cells. Without the ability to form new blood vessels, tumor size would be limited to 2 mm. Tumors express the growth factors that stimulate the angiogenic process.

    The Angiogenesis Process

    • Creating blood vessels is a complex process. Growth factors produced by the tumor enter neighboring tissue and bind to receptors located on existing blood vessels, according to the Angiogenesis Foundation. Surface cells activated by the receptors send chemical signals to the cell nucleus, which releases enzymes that dissolve the basement membrane, or a covering surrounding the blood vessels. The blood vessel cells divide and migrate through the spaces created by the enzymes toward the tumor, forming a sprout. More enzymes on the tumor dissolve the tissue in front of the sprout as it grows toward the tumor. As the sprout extends, the cells roll to form a tube. Muscle cells form to support the new blood vessel, completing the process.

    Angiogenesis Inhibitors

    • Angiogenesis inhibitors disrupt the cascade with the intent of halting or slowing tumor growth. These agents do not attack the cancer cells directly. Three classes of inhibitors each focus on a different aspect of the process. Matrix metalloproteinase (MMP) inhibitors interfere with the action of the enzymes that dissolve the basement membrane. Endothelial cell inhibitors prevent the division of blood vessels that then migrate toward the tumor. The third class, called angiogenesis activation inhibitors, interrupts the angiogenesis cascade. Bevacizumab (Avastin) is the only angiogenesis activation inhibitor approved by the Food and Drug Administration for cancer treatment.

    Future Research

    • Angiogenesis inhibitors have a modest effect on survival when used for patients with certain types of advanced cancers, according to the National Cancer Institute. These agents are also being explored for use in earlier stages of cancer. Tumors tend to develop resistance to angiogenesis inhibitors, however, and increase production of growth factors not affected by the specific angiogenesis inhibitor used.

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