Medulloblastoma (MB) is the most common malignant brain tumor in children. Even with an aggressive regimen of surgery, radiation and chemotherapy, one-third of medulloblastoma patients still die from their disease. Moreover, those who survive suffer devastating side effects from the treatment, including cognitive deficits, endocrine disorders and an increased incidence of secondary cancers later in life. Novel approaches to therapy are desperately needed, and these are likely to come from a deeper understanding of the cells that drive tumor formation – the cancer stem cells. The goal of our research is to identify a potent new drug that targets the medulloblastoma cancer stem cell in preparation for the development of a cancer stem cell-dependent targeted therapeutic agent, termed a Disease Candidate, for a future Phase I clinical trial for recurrent medulloblastoma. We will also perform genomic experiments on CSCs which will identify those MB patients most likely to respond to this new drug.
It should be noted that Cancer is the leading cause of death in children in the industrialized countries between the ages of 2 and 14 years of age. As stated above, brain tumors are the most frequently diagnosed solid tumor in children and medulloblastoma is the most frequent malignant brain tumors diagnosed in children. Taken together these epidemiologic results suggest that the treatment of childhood cancer represents a huge unmet medical need in the state of California and throughout the USA. If we can develop a stem cell based targeted therapeutic approach to this form of embryonal cancer in children we should be able to do so for other embryonal tumors in children. This stem cell targeted therapy is likely to be less toxic to our pediatric patients compared to high dose chemotherapy and radiation which has significant long term morbidity. As a result, the severe neurocognitive sequelae associated with high-dose radiotherapy can be avoided and these children will be able to lead more normal lives.