Stem cell differentiation therapy for melanoma using human experienced drugs

Funding Type: 
Early Translational I
Grant Number: 
ICOC Funds Committed: 
Public Abstract: 
In 2008, the American Cancer Society estimates that in this country alone approximately 8,420 deaths will occur from melanoma and another 62,480 cases of melanoma are expected to be diagnosed. For the most advanced cases of melanoma, called Stage IV metastatic melanoma, the five year survival rate is 8 percent. Only two FDA-approved treatment options exist, dacarbazine and interleukin-2, and they have little success in treating this disease. Other than dacarbazine, which was introduced in 1975, and interleukin-2, no new drugs have been successfully developed in part because the specific mechanism of action of melanoma metastases is unknown. However, recent scientific studies have identified possible clues as to how this disease evolves; suggesting certain biological targets in stem cell pathways are instrumental to the disease’s genesis and progression. This research has also revealed that known FDA-approved drugs for other indications act upon these stem cell pathways in such a way that melanoma cancer cells may be differentiated toward a more normal, less proliferative cell state. Finding FDA-approved drugs for other indications that also work in metastatic melanoma will speed drug development and clinical trials to provide a therapy to patients quickly. A recent clinical study of one of these FDA-approved drugs demonstrated efficacious effect in 40 percent of the melanoma patients, including an observation of complete suppression of the disease. We now need to translate these research discoveries and clinical observations to support the development of new therapeutic options for metastatic melanoma. This CIRM Translational Research grant will leverage and utilize these recent scientific discoveries in two ways: 1) by supplying resources to allow for our advanced technological approaches to better understand stem cells’ mechanistic role in this disease; and 2) to quickly identify and develop new IND-ready therapies for this disease by capitalizing on the identity of chemical classes of those FDA-approved drugs and other human experienced compounds identified in these previous studies. This CIRM supported grant will have the opportunity to discover and develop new medicines for a disease that will have an immediate, near term beneficial impact for California citizens.
Statement of Benefit to California: 
Of the 62,480 cases of melanoma expected to be diagnosed this year, one in six will be in California. Approximately 20 Californians per week will die this year from melanoma. Estimates of melanoma treatment costs alone averages more than $740 million and may exceed $1 billion each year in the United States [REDACTED]. The treatment cost for California will approach $200 million. If other costs such as complication risks and economic workforce losses were factored into the analysis, the cost would be several times higher. Late-stage melanoma patients have the most expenses for treatment and have little therapeutic options. About 90 percent of the total annual direct costs for treating melanoma is spent on those with advanced disease. Finding a cure for metastatic melanoma would deliver direct life-saving benefits to thousands of patients and needed economic support to the state of California. Utilizing our advanced clinical approach and research in metastatic melanoma would also fulfill the CIRM mandate to deliver highly effective therapies based on stem cell biology within a short time frame to benefit the health of Californians and the world.

© 2013 California Institute for Regenerative Medicine