Angiogenesis Discovery Points to Novel Therapy for Multiple Diseases

Tatiana Byzova, PhD, a faculty member in Lerner Research Institute's Department of Molecular Cardiology and Director of the Center for Angiogenesis Research, and colleagues have discovered a fundamental biological pathway in angiogenesis (formation of blood vessels), published online October 3, 2010 in Nature (DOI: 10.1038/nature09421). The significance of this discovery is summarized by Dr. Byzova, in that "it affects many biological processes - from wound healing to aging."

Some pathologies included in that spectrum are age-related macular degeneration, atherosclerosis, and rheumatoid arthritis, while their published data indicate a particularly notable role in cancer. The results of this advanced understanding point to an exciting new approach for novel therapies.

In 1989, a protein called vascular endothelial growth factor (VEGF) was identified as a trigger of angiogenesis. This discovery led Genentech to develop the first effective treatment for macular degeneration; related work contributed to the development of a drug to block VEGF function in cancer, essentially starving the tumor of the nutrients the blood would otherwise bring.

However, although many tumors respond to anti-VEGF treatment, most develop resistance to the therapy and continue to survive over time. One possible explanation is that VEGF is not the only trigger leading to angiogenesis. This is precisely what Dr. Byzova's team has found.

Dr. Byzova's research has identified a class of oxidized lipids that are abundantly present in highly vasculated tumors. Further interrogation parsed out the process through which these products induce new blood vessel formation. It appears that cells use a family of receptors previously known to recognize foreign products such as bacteria to sense and respond to the danger of oxidation. The results point to a novel therapy that may well be an alternate way to starve the tumors that have managed to survive despite VEGF inhibition. Through uncovering a potential way to get around tumor resistance to VEGF, Dr. Byzova's group has opened up new doors for developing treatments for cancer. The fundamental discovery also provides substantial insight for novel treatments for other diseases that involve inflammation, oxidative stress, and angiogenesis.

Overall, this foundational discovery of a novel mechanism of angiogenesis comes just one year after Dr. Byzova headed a study that pioneered the identification of a new genetic-based human disease, published in Nature Medicine.