Harold F. Dvorak
Beth Israel Deaconess Medical Center
Massachusetts

Angiogenesis and Tumor Growth

For many years, cancer treatments have focused on medicating the symptoms of cancer, either through surgery to remove the tumor and surrounding tissue, or via radiation and chemotherapy protocols that kill malignant cells.

However, despite significant improvements in traditional cancer therapies, none of these treatments has been completely effective at curing common breast, prostate, and colon cancers. Some have significant side effects, damaging healthy tissue by radiation and chemotherapy.

NFCR Fellow Expertise

To address the flaws of conventional cancer treatments, Dr. Harold Dvorak, the Chief of Pathology at Boston's Beth Israel Deaconess Medical Center at Harvard University, is using support and sponsorship from the National Foundation for Cancer Research to understand tumor biology and the process that cancer cells use to metastasize, or spread from their primary location to other parts of the body.

NFCR Research Overview

Like all living tissues, cancer tumors need a steady supply of blood to survive. So as a part of his research into tumor biology, Dr. Dvorak focuses on angiogenesis, the process that malignancies use to generate the new blood vessels they need to grow and spread. Dr. Dvorak believes that if he can stop the mechanism by which tumors acquire additional blood vessels, he could prevent tumor growth or metastasis and literally starve tumors to death.

NFCR Research Findings

In research supported by NFCR, Dr. Dvorak has pinpointed a molecule called vascular endothelial growth factor-or VEGF-that causes cancer tumors to emit a clotting agent that encourages and supports the growth of new blood vessels. Just as a wound forms a clot to begin the healing process, Dr. Dvorak has discovered that cancerous tumors are able to turn on this same healing mechanism for their own purposes.

According to Dr. Dvorak, cancerous tumors make and secrete VEGF that causes blood vessels to leak plasma fibrogen, the substance that helps form blood clots. This in turn, enables the growth of the new blood vessels that the tumor needs to grow. However, tumors differ from healing wounds in one important respect. As soon as a wound is healed, VEGF production is turned off abruptly. Tumors, on the other hand, continue to make large amounts of VEGF and in essence keep the body's healing mechanism in the "on position," allowing malignant cells to grow and spread at rapid speed.

This process is a major factor in breast cancer, as breast cells overproduce VEGF even before they become cancerous. Therefore, preventing VEGF overproduction could arrest breast cancer before it can invade healthy cells and metastasize to other parts of the body.

Impact on Cancer Prevention, Treatment, or Cure

To grow beyond minimal size, cancer tumors must induce a new blood supply through angiogenesis. By understanding the many steps and mechanisms involved in tumor angiogenesis, Dr. Dvorak's research will likely have practical value in terms of identifying specific steps for therapeutic intervention. This research progress offers hope for angiogenesis-centered treatments that will halt tumor growth, and that could potentially shrink the size of existing tumors.