Developing chemotherapy for diffuse pontine intrinsic gliomas (DIPG)

摘要

Highlights ? New WHO glioma classification of diffuse midline glioma with H3 K27M mutation calls for a biopsy of diffuse intrinsic pontine glioma (DIPG). ? Biological characteristics of DIPG are different from supratentorial high grade glioma. ? Monoclonal antibodies and target inhibitors are on-going clinical trials. ? Spontaneous DIPG animal model using RCAS/tv-a seems to be promising. ? Recent advancement of convection enhanced delivery technique could solve drug delivery problem in DIPG. Abstract Prognosis of diffuse intrinsic pontine glioma (DIPG) is poor, with a median survival of 10 months after radiation. At present, chemotherapy has failed to show benefits over radiation. Advances in biotechnology have enabled the use of autopsy specimens for genomic analyses and molecular profiling of DIPG, which are quite different from those of supratentorial high grade glioma. Recently, combined treatments of cytotoxic agents with target inhibitors, based on biopsied tissue, are being examined in on-going trials. Spontaneous DIPG mice models have been recently developed that is useful for preclinical studies. Finally, the convection-enhanced delivery could be used to infuse drugs directly into the brainstem parenchyma, to which conventional systemic administration fails to achieve effective concentration. The WHO glioma classification defines a diffuse midline glioma with a H3-K27M-mutation, and we expect increase of tissue confirmation of DIPG, which will give us the biological information helping the development of a targeted therapy.