[Nucleoside analogs in the treatment of primary malignant brain tumors].
Standard therapeutic modalities including surgery, radio- and/or peripheral chemotherapy are ineffective in malignant gliomas. This is due to infiltration of distant brain areas by glioma cells and to the blood-brain barrier limiting penetration of anticancer drugs. One of the most promising experimental methods of glioma therapy is intracerebral implantation of biodegradable polymers containing cytotoxic compounds. This method allows to avoid peripheral toxicity of drugs. Considering that practically it is only malignant cells that proliferate in the brain, the use of drugs displaying selective toxicity toward DNA-replicating cells might help to avoid central toxicity as well. Several nucleoside analogs display selective cytotoxic and/or radiosensitizing effects on proliferating cells. Despite encouraging results obtained in the in vitro and animal models of gliomas, peripheral administration of these drugs turned out to be ineffective in the clinical settings. Intracerebral implantation of nucleoside analogs-containing biodegradable polymers may be much more efficacious, especially when combined with radiotherapy. Appropriate nucleoside analogs may also be employed in cell-selective radiotherapy and gene therapy of malignant gliomas.
Pracowni Farmakologii Doświadczalnej Instytutu Medycyny Doświadczalnej i Klinicznej Polskiej Akademii Nauk im. M. Mossakowskiego. tkryczka@cmdik.pan.pl
Tomasz
T
Kryczka
Paweł
P
Grieb
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000532:radiotherapy*; D006801:Humans; D009705:Nucleosides / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D009705:Nucleosides