The Effect of Masitinib on Pediatric Glioblastoma

Abstract

Tumors of the Central Nervous System are the most prevalent pediatric solid tumor with gliomas being the most common and most aggressive form. The current standard of care involves a combination therapy with chemoradiation and gross tumor resection. The five-year survival rate of pediatric brain tumors is upwards of 70%, however, the combination of chemotherapy and radiation has proved to be harmful, especially to children, and in many cases significantly reduces their overall quality of life physically, socially and cognitively. As a result, finding ways to increase the efficacy of chemotherapy and/or radiation without increasing dosing is paramount in order to increase the life quality of survivors. Using a mouse model, this study investigated masitinib, a tyrosine kinase inhibitor, as a single agent and in combination with temozolomide, the current standard of care DNA alkylating agent, in the treatment of pediatric glioblastoma. This involved injection of patient derived pediatric glioblastoma xenografts into athymic nude mice and subsequent treatment of the mice with masitinib and/or temozolomide. Any possible chemosensitizing effects masitinib may have in a pediatric brain tumor xenograft model were also evaluated. The rationale for this combination is based on masitinib’s ability to effectively cross through the blood brain barrier and inhibit cell division in other types of cancer. While results indicated that masitinib does not work well as a single agent, it may in fact have cted as a chemosensitizer towards temozolomide, providing increased tumor growth delay relative to either drug used as a monotherapy. This finding warrants further investigation of masitinib in combination with temozolomide against pediatric glioblastoma.