Project leader: Lucienne Ronco, Ph.D.
Key collaborators: Bill Hahn, M.D., Ph.D.; Levi Garraway, M.D., Ph.D.; Todd Golub, M.D.; David Takeda, M.D.; Marius Pop, Ph.D.

More than half of all prostate cancers harbor an abnormal combination of two genes, which, normally separate, become fused together in cancer cells. Because of this gene fusion, one of the participating genes, called ERG, becomes permanently turned on, constantly signaling cancer cells to grow. These findings underscore ERG as an important therapeutic target in prostate cancer.

Although ERG is a highly promising drug target, it is also a highly challenging one. ERG functions as a transcription factor – an important class of molecules that directly regulate genes. Transcription factors are widely considered “undruggable” because pharmaceutical companies do not know how to develop drugs against them.

To address this challenge, Broad Institute scientists are pursuing a comprehensive and innovative drug discovery program aimed at ERG. They have created the initial tools needed to begin screening collections of chemical compounds and will begin searching for compounds that can directly bind to ERG and/or interfere with its function.