Ichiro Nakano, M.D., Ph.D., Clinical Instructor / Assistant Professor,
Departments of Neurosurgery, Pediatrics, and Psychiatry, David Geffen School of Medicine at UCLA
2008
Despite the dramatic improvements in the outcome of other childhood cancers in the last decades, brain tumors remain the leading cause of death in the pediatric oncology. Malignant brain tumors are composed of heterogeneous cell populations. Recent investigations, including our own, have identified a stem cell population, called ‘brain tumor stem cells (BTSC)’. These malignant stem cells proliferate and form the entire tumor mass. Initially, we hypothesized that targeted therapeutic strategies, which exploit molecular differences present within a heterogeneous population of brain tumor cells, will lead to the specific eradication of BTSC without causing toxicity. With excellent support by the Childhood Brain Tumor Foundation, we could perform several lines of experiments and successfully identified a transcription factor, FOXM1, as a critical gene to regulate survival and proliferation of BTSC. We then screened our small molecule libraries, available for the clinical researchers at UCLA Neurosurgery, to identify specific inhibitors for FOXM1. Recently, we were extremely excited with the fact that several compounds, approved by the Food and Drug Administration, selectively inhibit the action of FOXM1 in pediatric brain tumors and their stem cells in culture. We are now in the process of designing pre-clinical and clinical trials for pediatric brain tumors with the identified new chemotherapeutic agents.
Considering the limited effects of the current therapies on malignant brain tumors, multiple parallel or compensatory oncogenic pathways exist to allow tumor stem cells to escape and survive. Thus, it is unlikely that a single agent therapy can cure malignant brain tumors, and multiple molecularly-targeted therapies are crucially required to terminate malignant brain tumor growth. Given that in mind, we will continue to seek revealing the entire key signaling mechanisms underlying BTSC survival and proliferation.
Novel strategies targeting molecular aberrations will eventually offer innovative therapeutic approaches for patients with brain tumors. The findings we have obtained by the grant support by the CBTF and will obtain in the future will serve as a rationale to stratify patients in future clinical trials. Along the path, our mission is to make a concrete impact on future prognoses of pediatric patients with these devastating tumors.
I Am Chosen