Cancer trails only cardiovascular disease as the leading cause of mortality in the US. Except for some germ cell cancers, leukemias and lymphomas, once a cancer has spread it generally becomes an incurable disease. Although currently available therapies can produce shrinkage in many types of tumors, these effects are transient and the vast majority of people with disease that has spread from the original tumor succumb to their cancer. It is clear that new approaches are needed to treat these diseases. Laboratories have begun to apply the principles of stem cell biology to understand the biology of the cancer cells found in solid tumors. Recently, it has been found that in tumors arising in the breast, colon, pancreas and head and neck, only a subset of the cancer cells, called cancer stem cells, can establish tumors in a immunodeficient mice. These cancer stem cells are responsible for the growth and spread of the tumor and ultimately for a patient’s death. The ability to prospectively identify tumorigenic cancer cells isolated directly from a patient's tumor will facilitate the identification of pathways that regulate their growth and survival in patients. Since these cells drive tumor development, targeting them will lead to more effective therapies. The goal of this grant is to develop model systems and a reagent base so we can identify new therapeutic targets to eliminate these cancer stem cells.
This grant has great potential to benefit the people of California. Accomplishing the goals of this proposal could lead to new treatments for cancers that originate in epithelial organs such as the breast and colon. Such tumors are the leading cause of cancer-related deaths. Furthermore, these cancers and their treatments lead to much pain and suffering that may be alleviated by better treatment options. Current therapies for localized cancers of the breast and colon often include chemotherapy and radiation. Both of these treatment modalities cause many serious side-effects including pain, fatigue, occasional disfigurement and sometimes even death. Furthermore, these modalities are only modestly effective for treating early stage cancer, and have only a minimal impact on survival for patients whose cancer has spread from the site of origin. This proposal has the potential to identify new therapeutic targets for drugs that are more effective and less toxic. Secondarily, this proposal should have economic benefits. Improvements in cancer therapies will result in less work loss by affected individuals. Finally, the identification of more effective cancer therapeutic targets and improved models for testing them will lead to new employment opportunities for the people of the state.