NFCR Basic Research in Action: Angiogenesis

Angiogenesis is the formation of new blood vessels.

The process involves the growth of endothelial cells, which line the inside walls of blood vessels.

Angiogenesis is a normal and vital process in growth and development, but it also plays a role in several diseases, including cancers.

A blood supply is necessary for tumors to grow beyond a few millimeters in size and transition from a benign state to a malignant one. In other words, angiogenesis is a cause for concern with tumors because it feeds and sustains them.

Without a proper blood supply, a tumor wouldn’t be able to grow beyond a certain size or spread, so scientists are establishing the most effective ways to block tumor angiogenesis.

Historical Perspective of Angiogenesis

Dr. Harold F. Dvorak, who received NFCR funding for over 30 years, discovered that tumor cells secrete a vascular endothelial growth factor (VEGF) and this discovery provided the molecular basis for the field of angiogenesis. Dr. Dvorak’s discovery helped pave the way for research on anti-angiogenesis treatments that can halt and even reverse tumor growth.

In 2004, the first VEGF-targeting anti-angiogenic drug Avastin® was approved by the FDA for the treatment of colorectal cancer, and, today, in addition to colorectal cancer, Avastin is approved for the treatment of non-small cell lung cancer, renal cell carcinoma (a type of kidney cancer), the aggressive brain cancer glioblastoma multiforme (GBM) and certain types of cervical and ovarian cancers.

Current NFCR Research

The seminal research of NFCR-funded scientist, Dr. Rakesk Jain, demonstrated that anti-angiogenic therapy works by normalizing the abnormal, leaky blood vessels that usually surround and penetrate tumors. This therapy improves the delivery of chemotherapy drugs, increases the oxygen content of cancer cells and makes radiation treatments more effective.

Dr. Jain and his team have identified molecular resistance pathways and characteristics that cause resistance to anti-angiogenic therapy. Their findings may direct the development of new drugs that target these pathways and could extend the benefits of anti-angiogenic therapies for patients.  The scientists focus on the role of angiogenesis in glioblastoma (GBM), the deadliest form of brain cancer. His research is developing the combined use of anti-angiogenic therapies and immunotherapy (immune checkpoint inhibitors) for GBM patients.

In collaboration, NFCR-funded scientists, Dr. Paul Schimmel and Dr. Xiang-Lei Yang, have determined that the vital protein synthesis enzyme, SerRS, shuts down angiogenesis in breast cancer by inhibiting the Myc gene, one of the main genes that controls the expression of VEGF. SerRS is likely a potent suppressor of cancer progression and metastasis. Their research may lead to novel therapeutic applications for breast, brain, rectal, esophageal, kidney, lung and liver cancers.

Translational Research

NFCR funding since 2008 helped Dr. Paul Fisher think “outside the box” to develop IL/24 gene therapy (IL/24 is from the Interleukin gene family of immune system modulators). He engineered IL/24 gene to reach cancer cells — at all sites in the body — to commit suicide (normal way cells die). Healthy cells are unaffected by IL/24 gene’s effects. IL/24 gene modulates the immune system to kill cancer, inhibits blood vessel formation (anti-angiogenesis) to tumors to starve them of vital blood supply, and sensitizes cancer to radiation, chemotherapy and immunotherapy. With NFCR translational funding, IL/24 gene therapy is advancing through pre-clinical research first as a new treatment for fatal brain cancer, GBM (glioblastoma). IL/24 gene therapy is effective in models of numerous types of advanced cancer including melanoma and colon, lung, bladder, prostate, liver, and pancreatic cancer, among other types.