Development of an Inhibitor of Glioblastoma Stem Cells

Funding Type: 
Early Translational II
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 

High rates of mortality convert malignant glioma into the third leading cause of cancer-related death among men 15-54 years of age and the fourth leading cause of death for women 15-34 years of age. Among children less than 15 years of age, the impact of central nervous system cancer is even more pronounced. Primary brain tumors are actually the most common solid tumor of childhood and the second leading cause of cancer death after leukemia. The toxicity of current treatments causes serious life-long effects in the very few patients who survive. However, glioma is not presently a primary research focus for pharmaceutical companies.
Recent research has found that gliomas are driven by a small group of cells inside the tumor that behave like stem cells. These cells have some of the same marker molecules on their surface as do normal nervous system stem cells. These “cancer stem cells” divide to produce most of the cells in a brain tumor, and they also divide to make more cancer stem cells. What makes these glioma cancer stem cells dangerous is that they invade normal brain tissue adjacent to the tumor and they are very resistant to standard chemotherapy and radiation therapy used to treat the brain cancer. So even though therapy might kill many of the cells in the brain tumor, the glioma cancer stem cells survive, continuing to divide and invade normal brain tissue. Therefore, a potentially very effective strategy may be to disrupt or destroy the glioma cancer stem cells.
There are molecules of central importance in nervous system stem cell biology. These molecules participate in the elaboration of tissue in the developing nervous system. They are found in very high levels in glioma cancer stem cells. We know that if we use genetic ways of blocking these molecules in glioma cancer stem cells, the gliomas won’t grow in experimental systems. Therefore our aim is to design and test a drug that inhibits these molecules as a way of suppressing glioma cancer stem cells and treating glioma.
Our approach to making a drug involves the use of the [REDACTED] supercomputer. A physicist on our team will use this computer and advanced computer programs to design chemicals that will bind to and inhibit a specific molecule in the glioma cancer stem cells. We will then make the chemicals and test them along with thousands of known chemicals. The tests will involve human glioma cells taken from brain cancer patients during surgery and grown in laboratory dishes. The chemical that is the most effective against the glioma cells, and which does not injure normal nervous system cells growing in laboratory dishes will be further developed as a drug for glioma that can be taken orally. This kind of cancer stem cell-based treatment would be completely new and has the potential for great benefit in brain cancer patients with fewer side effects than current chemotherapy and radiation therapy.

Statement of Benefit to California: 

The proposed research will benefit the people of California in several important ways. Initially, the CIRM grant would benefit [REDACTED] in terms of grant revenue, helping [REDACTED] cover expenses and perhaps keep a number of people employed. Also, additional scientists and scientific technical personnel at more junior levels would be hired for this grant. Hence the proposed project would provide training for younger scientists and technicians and help prepare them for successful careers in Academia and Industry. The [REDACTED] and the California stem cell program would gain major national and international recognition if a successful brain cancer drug were to be developed from the proposed project. This would contribute to regaining respect and esteem for the state and [REDACTED], thereby encouraging outside investment, at a time when the State has suffered economically.

[REDACTED] would largely own the patent rights to any drug developed by such a program, and if successful the drug could bring in moneys to the State via licensing or sublicensing to drug and healthcare companies worldwide. This revenue earning mechanism would be enormously amplified if the drug is effective in other stem cell driven cancers that express the target molecule including lung cancer, T-cell leukemia, melanoma and breast cancers. This often happens with successful anticancer drugs; initially they are targeted to a particular cancer and then are found to be useful in several cancers.

One of our long term goals with developing a brain cancer therapeutic is to create a successful drug company based in [REDACTED]. Such a company would provide jobs for local residents, and would provide tax revenue for the State. The company would earn income directly through sales of the drug or via sales coupled with sub-licensing agreements. A large successful company of this nature based in California would attract national and international attention to the local Biotechnology business environment.

Finally, a successful brain tumor treatment would profoundly benefit local California residents and suffering from this devastating illness. The majority of patients treated for brain tumors in California are California residents, and such a treatment would directly affect them and their families, friends and professional colleagues. If the drug proves to be active against lung, skin, breast or blood cancers the direct benefit in terms of medical treatment would be greatly expanded.