Development of An Innovative Treatment Strategy for Neuroblastoma and Other Pediatric Tumors: A Novel Phospholipid Ester Analogue and its Multifunctional Cancer-targeting Nanoconstruct

Neuroblastoma is one of the most common forms of cancer in childhood, and approximately 700 young children are diagnosed with this tumor each year in the United States alone. The disease is very aggressive, and despite various forms of treatment such as chemotherapy, radiation and surgery, more than one third of all patients with advanced-stage disease will eventually die. The patients who survive are stricken with the long-term side effects of highly toxic treatments. Thus, more targeted therapies that kill the cancer but spare healthy tissue are urgently needed. The novel small molecule NM404 is highly selectively taken up by cancer cells but minimally affects healthy tissue. This compound is currently being evaluated in a radioactive form as an imaging agent at the University of Wisconsin. However, NM404 seems to also be able to kill cancer cells in higher doses. We will perform pre-clinical tests to find out if NM404 can kill neuroblastoma or other forms of childhood cancer and to evaluate if this compound could be a new, potent treatment drug.  In the second part of our proposal we will use NM404 to guide nano-sized particles to cancer cells. Nanoparticles are programmed to attack and destroy cancer cells. This relatively new area of science is called cancer nanotechnology. We believe that combining NM404 with cancer nanotechnology has the potential to lead to a new, powerful, multifunctional drug compound capable to significantly improve the survival for neuroblastoma and other childhood cancer patients.