Grant: Project Grant

Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children and adolescents, with the majority of cases arising in children under the age of 10 years. Following the successful treatment of the initial disease, recurrence manifests in approximately one-third of patients, with about 80% of recurrences localized at the primary tumor site. Unfortunately, with current treatments, the 5-year survival rate for these patients is only 17-28 %. In addition, due to the characteristic toxicities associated with some anti-cancer drugs for RMS, treatment of these young patients can lead to a series of long-term health complications in adult life including neurological and cardiac disorders. The current research project describes the development of a nanoparticle (termed a liposome) containing the anti-cancer drug, vinorelbine. This drug works by preventing the cancer cells from dividing and ultimately leads to cell death. Liposomes containing various drugs are currently used in the treatment of several cancers. Our liposome nanoparticles have been specially designed such that the drug is released when the temperature exceeds that of normal body temperature. We will achieve localized release of the drug at the tumor site by increasing the temperature of the tumor using an ultrasound machine. This technique will increase the amount of drug delivered specifically to the tumor site and therefore minimize drug exposure to normal tissues. We will also investigate whether the combination of vinorelbine and an increase in the temperature of the tumor has a greater tumor killing effect compared to vinorelbine alone. The potential benefits of this project for RMS patients are a greater killing effect of recurrent RMS tumors and a reduction in the short and long-term side effects, which are commonly associated with exposure of chemotherapy to normal tissues.