Glioblastoma multiforme y estudio de la resistencia a la quimioterapia mediada por transportadores ABC / Study of resistance to chemotherapy mediated by ABC transporters in biopsies of glioblastoma multiforme

ABSTRACT

Background: Mortality rate is dramatically high in high grade brain tumors. The presence of multiple drug resistance transporters in glioblastoma multiforme, has contributed largely to the poor effcacy of targeted therapy against cancer in the central nervous system. Aim: To analyze the percentage of survival and mortality of patients with glioblastoma multiforme in a cohort of patients in Chile and to co-rrelate the chemo-resistance of these cells with the expression level of multiple drug resistance transporters. Materials and Methods: Eighteen biopsies of glioblastoma multiforme were obtained from patients at the Institute of Neurosurgery Dr. Asenjo (INCA). The tumor cells were obtained from primary cultures and the expression and activity of multiple drug resistance transporters was assessed by RT-PCR and immunohistochemistry. Population-based study was performed using the databases of the Department of Neurosurgery of INCA. Results: The number of patients with glioblastoma multiforme increased between 2007 and 2009, from 3.5 percent to 7.9 percent of total brain tumors. Mortality of these tumors is 90 percent at three years. A high expression and activity of the multiple drugs resistance associated protein 1 (Mrp1) transporter was observed in primary cultures of biopsies. Conclusions: We propose that Mrp1 activity is responsible for the chemo-resistance of the glioblastoma multiforme and inhibition of this transporter could represent a plausible strategy for the treatment.