"Our increased understanding of SHH-associated tumors has recently led to the development of drugs that specifically inhibit the SHH pathway. Early studies in humans with these new drugs have offered some hope for patients, but many do not respond and most patients who do respond develop resistance to the drug. For this reason, it is essential to develop alternative, or additional, therapies that are more effective than current treatment options," Wechsler-Reya said.
The team's first set of experiments used a mouse model for SHH-dependent medulloblastoma. In-vitro studies of mouse tumor cells showed that cell-cycle inhibitors caused tumor cell death. In vivo, mice that were treated with the inhibitor had smaller tumors that weighed less compared to mice that were not treated, essentially halting the progression of the tumor.
The second set of experiments used human SHH-dependent medulloblastoma cells. When the researchers treated these human tumor cells with cell-cycle inhibitors, they also observed a significant reduction in tumor growth and progression.
Finally, when the scientists combined SHH inhibitors with cell-cycle inhibitors, they found that the combination worked together to produce results that were greater than either inhibitor alone.
"These results strongly support an approach to treatment that combines SHH inhibitors with cell-cycle inhibitors to treat medulloblastoma. Our hope is that the combination of these inhibitors will prevent tumor progression and drug resistance, and improve the overall effectiveness of curr
|Contact: Susan Gammon, Ph.D.|
Sanford-Burnham Medical Research Institute