Causes of drug resistance and novel therapeutic opportunities for the treatment of glioblastoma

Malignant gliomas are among the most lethal and intractable of human tumors and drug resistance is one of the major obstacles to their successful trea tment. Recent advances in the molecular biology and genetics of human cance rs provide a detailed understanding of cellular and molecular responses to chemotherapy and how drug resistance may develop. Several oncogenes and tum or suppressor genes have been shown to confer resistance to tumor cells and should, therefore, provide novel and defined targets for cancer treatment. In addition to overcoming cellular resistance, special efforts to increase drug delivery to glial tumors need to be pursued because of the relatively unique problem of the blood-brain barrier. Treatments aimed at these targe ts will likely benefit from combined therapies including surgery, tradition al chemotherapy and targeted disruption of other physiological processes su ch as angiogenesis.