||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.