Mechanisms of Brain Tumor Chemoresistance

National Institute Of Neurological Disorders And Stroke

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Abstract

We previously reported that stathmin, a microtubule destabilizer required for the progression of cells through the cell cycle, also mediates the motility, migration, and invasion of malignant glioma cells. This was shown in experiments in which stathmin levels were experimentally increased or decreased with resulting changes in these cellular functions. We also demonstrated that nitrosoureas, DNA alkylating and protein carbamoylating drugs that inhibit stathmin and that are traditionally thought to inhibit only cell division, also inhibit motility, migration, and invasion. As invasion of surrounding brain by malignant glioma cells is one of the major causes of morbidity and mortality for patients with malignant glioma tumors, we have continued pursuing strategies to inhibit stathmin function in vivo, alone and in combination with nitrosourea therapy.