Moreover, the comparison of gene signatures revealed that rapamycin's effectiveness was due in part to its action on a molecule that causes cancer cells to self-destruct.
The method also enabled researchers to match up a pair of natural products, known as celastrol and gedunin, with a mechanism by which some advanced prostate tumors continue to grow aggressively despite hormone-blocking treatments. A paper in Cancer Cell reports on this work, which made it possible for scientists to connect the action of the two natural products with known biological effects of other drugs. It turned out that celastrol and gedunin inhibit a molecule called HSPH90, which in turn blocks the overactive cell signaling of the androgen receptor in prostate cancer cells that drives their aggressive growth. Dana-Farber researcher Haley Hieronymus, PhD, who used the Connectivity Map to sift through thousands of drugs and compounds, is the paper's lead author.
The researchers said that in view of these promising results, they are proposing a large-scale effort -- along the lines of the Human Genome Project -- to map connections among genes and diseases to accelerate the development of new and improved therapies for a wide range of disorders. Like the data in the current papers, the information garnered in the course of such a project would be freely available to scientists everywhere.
Source:Dana-Farber Cancer Institute