Brainstem tumors represent 10-15% of pediatric
central nervous system tumors and
diffuse intrinsic pontine glioma (
DIPG) is the most common
brainstem tumor of childhood.
DIPG is almost uniformly fatal and is the leading cause of
brain tumor-related death in children. To date,
radiation therapy (RT) is the only form of treatment that offers a transient benefit in
DIPG. Chemotherapeutic strategies including multi-agent
neoadjuvant chemotherapy, concurrent
chemotherapy with RT, and
adjuvant chemotherapy have not provided any survival advantage. To overcome the restrictive ability of the intact blood-brain barrier (BBB) in
DIPG, several alternative
drug delivery strategies have been proposed but have met with minimal success. Targeted
therapies either alone or in combination with RT have also not improved survival. Five decades of unsuccessful
therapies coupled with recent advances in the genetics and biology of
DIPG have taught us several important lessons (1).
DIPG is a heterogeneous group of
tumors that are biologically distinct from other pediatric and adult high grade
gliomas (HGG). Adapting
chemotherapy and targeted
therapies that are used in pediatric or adult HGG for the treatment of
DIPG should be abandoned (2). Biopsy of
DIPG is relatively safe and informative and should be considered in the context of multicenter clinical trials (3).
DIPG probably represents a whole
brain disease so regular neuraxis imaging is important at diagnosis and during
therapy (4). BBB permeability is of major concern in
DIPG and overcoming this barrier may ensure that drugs reach the
tumor (5). Recent development of
DIPG tumor models should help us accurately identify and validate therapeutic targets and small molecule inhibitors in the treatment of this deadly
tumor.