About this Research Topic
Glioblastoma multiforme (GBM) is an aggressive and fatal disease with less than 2% of patients surviving 5 years without tumor recurrence after initial diagnosis and treatment. Concerted efforts have been made towards drug development and novel therapeutic approaches for glioblastoma, yet the progress is limited and the prognosis for the patients with GBM remains poor. Inherent or acquired resistance to available therapies, regional and heterogeneous blood-glioma barrier, and the population of stem-like cells within glioblastoma present challenges that are being aggressively addressed. In particular, advances have been made in understanding the molecular biology of glioblastoma, resulting in a number of new treatment modalities, including tyrosine kinase inhibitors, angiogenesis inhibitors, gene-, viro- and immuno-therapies. In addition, the emphasis has been to define sensitizing strategies that may potentiate efficacy of existing chemo- or radio-therapies.
Induction of DNA damage and deregulation of DNA repair pathways is the hallmark of current approaches of chemo- and radio-therapy, and gene expression or mutation profile has been in focus to intense analyses aimed at defining new therapeutic targets. A focused (or whole genome) siRNA screens have been instrumental in identification of several druggable targets. Similarly, multifaceted approach to measure DNA repair capacity in tumor cells has been developed and may have wide clinical implications especially to determine sensitivity to genotoxic drugs. Bi-allelic mutation in IDH1 found in secondary GBM cause deficit of NAD+, trigger production of onco-metabolite 2-hydroxy glutarate now have been found associated with compromised homologous recombination ability and synthetic lethality of PARP inhibitors. However, evidence from more recent publications indicate that PARP inhibition may not be suitable for IDH mutants especially in combination with alkylating agents. Prospective discussion of these relatively newer findings may shape the future directions for biomarker strategies for chemo- and radio-sensitizers.
This Frontiers Research Topic shall provide a platform for active discussion and summarize current knowledge of blood-brain barrier, cancer metabolism, cell signaling and genetic, epigenetic regulation of drug sensitivity/resistance, and offer new perspectives on developing novel therapeutic approaches and biomarkers for glioblastoma. We welcome high-quality original research articles, brief reports, as well as opinion, hypothesis, and review articles, and especially encourage submissions from early-career scientists.
Keywords: GBM, Blood-brain barrier, drug resistance, sensitizing therapies, DNA damage, onco-metabolites
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