According to a study conducted by scientists from the Johns Hopkins University School of Medicine in Baltimore and the University of Washington/Children's Hospital, medulloblastomas are initiated and maintained by inappropriate activity of the Hedgehog pathway by mutation.
To test the role of Hedgehog pathway signaling in medulloblastoma growth, cyclopamine, a plant-derived pathway inhibitor, was administered to cultured mouse and human medulloblastoma cells, and mice carrying this type of brain cancer. The results from this study indicate that inhibition of Hedgehog signaling turns off the mutated pathway and causes significant shrinkage and death of tumor cells without any evident detrimental effects on normal brain cells or other cells and organs.
This study shows that uncontrolled activity of certain signaling pathways, such as that regulated by Hedgehog, plays a key role in the establishment and growth of certain cancers. This approach of targeting a specific signaling pathway is relatively novel and holds the promise of directed therapies, potentially with fewer of the side effects commonly experienced with traditional chemotherapeutics. Hedgehog signaling has also been shown to be inappropriately activated in other tumors, such as basal cell carcinoma, pancreatic cancer, and other solid tumors.
Curis Inc has identified a number of additional Hedgehog pathway inhibitors and is exploring their further development as potential anticancer therapies.
"Curis' approach to drug development, based upon understanding how cells communicate with each other to sustain their development and growth is further validated by this study. We are developing targeted therapies that are intended to either disrupt this communication, as with cancer, or enhance it to foster the human body's natural repair processes," said Daniel R. Passeri, President and Chief Executive Officer of Curis. "We are pleased with the progress being made, and the results of this study provide us with promising data for the potential development of cancer therapies for medulloblastoma as well as other more common cancers."