Overcoming therapeutic resistance in malignant gliomas: current practices and future directions.

摘要: Abstract Malignant gliomas remain among the most treatment-refractory tumors. Traditional upfront treatment regimens have incorporated nitrosurea-based chemotherapy. This strategy has evolved to include temozolomide-based approaches. Promising Phase I/II data with TMZ in recurrent setting prompted a III EORTC study of combination RT for patients newly diagnosed GBM. The landmark 26981-22981/NCIC CE3 demonstrated significant improvement not only median survival, but also terms 2-year survival. Given that over one-quarter enrolled on + arm survived beyond 2-years, there appears be finite percentage who derive long-term benefit from this regimen. EORTC-based regimen represents an incremental standard care, rather than truly curative solution patients, further efforts must expended identify novel therapeutic To end, targeted therapies emerged as attractive option. Accumulating evidence suggests certain molecular pathways are selectively upregulated tumor vs. normal cells. Some these been shown instrumental proliferation, migration, invasion, angiogenesis, and/or survival preclinical models. These would appear represent ideal targets, their antagonism may lead ratio radiation. Emerging clinical studies "first generation" demonstrate select patients. Further molecular/genetic profiling undertaken exactly which benefit.