The status of the art of human malignant glioma management: the promising role of targeting tumor-initiating cells

Glioblastoma is the most prevalent and malignant form of brain cancer, but the current available multimodality treatments yield poor survival improvement. Thus, innovative therapeutic strategies represent the challenging topic for glioblastoma management. Multidisciplinary advances, supporting current standard of care therapies and investigational trials that reveal potential drug targets for glioblastoma are reviewed. A radical change in glioblastoma therapeutic approaches could arise from the identification of cancer stem cells, putative tumor-initiating cells involved in tumor initiation, progression and resistance, as innovative drug target. Still controversial identification of markers and molecular regulators in glioma tumor-initiating cells and novel approaches targeting these cells are discussed.

► Despite aggressive multimodality treatments glioblastoma prognosis remains poor.
► Progress of targeted drugs for the management of glioblastoma is disappointing.
► Glioblastoma stem cells contribute to tumor initiation, progression and recurrence.
► Drug targets include signaling pathways, perivascular, hypoxic and immune niches.
► The translational relevance of glioblastoma stem cell concept is challenging.