RESUMO
Despite the existence of a well described, succinct pathological grading system for gliomas, tumour behaviour between individual patients varies widely. In addition, predictors of response to treatment in glioblastoma multiforme are lacking. The majority of chemotherapeutic agents currently employed exert their effect on DNA. As our understanding of DNA repair mechanisms improves and predictive markers are elucidated, this may allow treating clinicians to individualise treatment based on molecular markers. This review examines important DNA repair mechanisms and their application to glioblastoma multiforme. By improving understanding of these mechanisms, and particularly the variations that occur between tumours and individuals, it may be possible to adapt treatment to maximise effectiveness and minimise toxicity.
Assuntos
Reparo do DNA/fisiologia , Tratamento Farmacológico/métodos , Glioma/fisiopatologia , Glioma/terapia , Animais , Humanos , Modelos BiológicosRESUMO
Clinical treatment decisions and the survival outcomes of patients with gliomas are directly impacted by accurate tumor classification. New and more reliable prognostic markers are needed to better identify the variable duration of survival among histologically defined glioma grades. Microarray expression analysis and immunohistochemistry were used to identify biomarkers associated with gliomas with more aggressive biologic behaviors. The protein expression of IQGAP1 and IGFBP2, when used in conjunction with the World Health Organization grading system, readily identified and defined a subgroup of patients with grade III gliomas whose prognosis was poor. In addition, in patients with glioblastoma multiforme, in whom IQGAP1 and IGFBP2 were absent, long-term survival of more than 3 years was observed. The use of these markers confirmed a nonuniform distribution of survival in those with World Health Organization grade III and IV tumors. Thus, IQGAP1 and IGFBP2 immunostaining supplements current histologic grading by offering additional prognostic and predictive information.