Phase I/II clinical trial targeting Hedgehog pathway in medulloblastoma cancer stem cells

Funding Type: 
Disease Team Therapy Planning I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

Medulloblastoma is the most common malignant brain tumor in children, and a major cause of pediatric cancer deaths. Research on medulloblastoma has uncovered the driving force behind cancer growth for a large proportion of these tumors. In about one third of medulloblastoma cases, a set of molecular signals called the “Hedgehog pathway” controls growth of the cancer stem cell, which is responsible for tumor propagation and resistance. Current treatment strategies to block the Hedgehog pathway are very promising, but resistance to the currently employed drugs develops quickly. We propose a clinical trial designed to target the Hedgehog pathway in medulloblastoma using a newly discovered inhibitor of Hedgehog pathway activity that should circumvent the problem of drug resistance. The Hedgehog pathway is like a key in a lock that opens the door to cancer stem cell growth. The current treatment strategy to treat this disease secures the lock, but the tumor cell often manages to pick the lock. Our proposed strategy secures the lock, and also wedges a stopper behind the door.

Medulloblastoma is an important disease afflicting children. The Hedgehog pathway is critical in not only medulloblastoma, but also a number of other cancers, including certain types of lung, prostate, skin, bladder and colon cancers. Establishing an effective clinical strategy to inhibit Hedgehog pathway activity in medulloblastoma will pave the way for treatment of many thousands of people suffering from multiple forms of cancer.

Statement of Benefit to California: 

Medulloblastoma, the most common malignant pediatric brain tumor, represents a significant health issue in children in California. The cost of treating just those children afflicted in California alone exceeds $50 million each year. In this proposal, we test a novel strategy to target a specific molecular cascade, the “Hedgehog pathway”, in the medulloblastoma cancer stem cell. Hedgehog pathway is known to be critical in the growth of approximately one third of medulloblastoma tumors, as well as in a number of other common human cancers. Successful completion of the proposed clinical trial will lead to improved outcomes in children with medulloblastoma, to healthier children in California, and to reduced medical and opportunity costs for the state. As a successful clinical strategy to target the Hedgehog pathway is relevant to many forms of lung, prostate, colon, skin and bladder cancer, this study will also pave the way for improved cancer therapy for thousands of Californians.