Laboratory of Judah Folkman, MD
Dr. Folkman’s laboratory team continues his important research, in the wake of his untimely death in January 2008. Following the recommendation of our Scientific Advisors, BCRF will continue to support this project.
In Memoriam: Judah Folkman (1933-2008)
Over the past year, Dr. Folkman's team has shown that have found that one of the normal functions of the breast cancer gene (BRCA1) is to maintain a normal level of thrombospondin-1, a protein that keeps
new blood vessels from growing into new tumors. They have further found that human breast cancers can prepare their future metastatic sites by secreting a novel protein, which lowers the level of thrombospondin-1 at the future metastatic site, such as lung.
The researchers have also discovered a small set of genes which are increased when microscopic in situ breast cancer switches on angiogenesis (i.e. recruits new blood vessels). One of these proteins is called HSP27, which is increased more than 20-fold (2000%) during the angiogenic switch.
During the coming year, the researchers plan to determine: (i) If it is possible to prevent the BRCA1 oncogene in its mutated, or overexpressed form from suppressing thrombospondin-1; (ii) To determine if is possible to prevent breast cancer cells from suppressing the production of thrombospondin-1 by the host tissue of a future metastatic site; (iii) If it is possible to prevent the angiogenic switch in breast cancer in part by blocking HSP27; and (iv) To determine the mechanism of action of Caplostatin.
Mid-Year Progress Report:
The Folkman group has been focused on investigating three different aspects of breast and ovarian cancer during this past funding period. First, they have been trying to understand how the breast cancer susceptibility gene, BRCA1, mutated in a subset of women with breast cancer, regulates blood vessel growth to cause expansion of tumor mass. Secondly, they have been investigating whether increased expression of a specific protein called heat shock protein-27 or HSP-27, may be an important trigger for the growth of breast cancer. They discovered that the HSP-27 gene was highly expressed in rapidly growing breast cancer cells as compared to breast cancer cells that are dormant or not actively growing. Third, the researchers have been examining whether breast and ovarian tumors may be effectively treated by a synthetic angiogenesis inhibitor discovered in the Folkman laboratory with a very broad spectrum of anti-cancer activity, called Lodamin. Lodamin is an improved version of the previously reported compound Caplostatin. Lodamin can to be administered orally rather than injected intravenously as was necessary with Caplostatin, thus making drug delivery much easier and less painful for patients.
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