Medulloblastoma 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 move a cancer stem cell-targeted therapeutic agent into a Phase I clinical trial for recurrent medulloblastoma. We will design the Phase I trial to include studies which will provide important information to inform this and future clinical trials designed to target the cancer stem cell.
Statement of Benefit to California:
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.
The CIRM Planning Grant in Childhood Brain Cancer, if awarded, will provide the initial resources required to implement a new paradigm for pediatric cancer therapeutics to target the tumor initiating stem cell population using a specific targeted therapeutic agent. The team approach is necessary to develop this Phase Ib trial along with the components necessary for its successful implementation. In summary, the benefits to the citizens of California from the CIRM disease specific grant for childhood brain cancer are;
1) Direct potential benefit to hundreds of children with medulloblastoma needing second line therapy
2) Financial savings to eliminate the toxicity and mobidity associated with lifelong side effects of high dose radiotherapy and chemotherapy on cognitive development.
3) New alliances between academia and industry for pediatric cancer therapeutics
4) This modality of therapy may apply to other pediatric cancers a large percentage of which have been shown to involve cancer stem cells.
5) Realization of CIRM mandate to deliver effective novel therapies within a short time frame to benefit the health of Californians afflicted with brain cancer.