Resent advances in chemotherapy for malignant brain tumors

Most malignant brain tumors are resistant to the chemotherapeutic agents because of the existence of several mechanisms or substances such as the blood-brain barrier, genes and proteins. Recently many studies have been started to overcome the chemoresistance. Especially recent advances in the field of molecular biology have contributed to examination of the chemosensitivities of tumor cells. Trials for the individualization of the treatment, so-called Taylor-made therapy, is one of these challenges. Loss of chromosome 1 p and 19 q is considered to be closely related to chemosensitivity in anaplastic oligodendrogliomas. This is one of the breakthroughs in the field of chemotherapy for malignant brain tumors. O6-methylguanine-DNA methyltransferase (MGMT) is a DNA repair enzyme which reduces the cytocidal effect of nitrosourea. In order to overcome the chemoresistance, drugs except nitrosourea or some drugs which reduce the MGMT activity are used for tumors expressing MGMT. New technology targeting growth factor receptor such as EGFR or VEGFR is also applied to cancer chemotherapy. On the other hand, multi-institutional cooperative studies have been started to obtain evidence in cancer treatment. Phase II study for a small number of patients is not sufficient to demonstrate the efficacy of the treatment and to establish the standard therapy. Multi-institutional randomized controlled study by JCOG Brain Tumor Study Group is the first trial for the treatment of malignant astrocytomas under well-established quality control and quality assurance systems. It can be a model of clinical trials for malignant brain tumors in Japan.