Abstract
Glioblastoma multiforme (GBM) is recognized as the most common and lethal form of central nervous system cancer. Currently used surgical techniques, chemotherapeutic agents, and radiotherapy strategies have done very little in extending the life expectancies of patients diagnosed with GBM. The difficulty in treating this malignant disease lies both in its inherent complexity and numerous mechanisms of drug resistance. In this review, we summarize several of the primary mechanisms of drug resistance. We reviewed available published literature in the English language regarding drug resistance in glioblastoma. The reasons for drug resistance in glioblastoma include drug efflux, hypoxic areas of tumor cells, cancer stem cells, DNA damage repair, and miRNAs. Many potential therapies target these mechanisms, including a series of investigated alternative and plant-derived agents. Future research and clinical trials in glioblastoma patients should pursue combination of therapies to help combat drug resistance. The emerging new data on the potential of plant-derived therapeutics should also be closely considered and further investigated.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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ATP Binding Cassette Transporter, Subfamily B, Member 1 / antagonists & inhibitors
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ATP-Binding Cassette Transporters / metabolism
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Allyl Compounds / therapeutic use
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Angiogenesis Inhibitors / therapeutic use
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Brain Neoplasms / drug therapy*
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Cell Cycle Checkpoints / drug effects
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Combined Modality Therapy
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DNA Modification Methylases / drug effects
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DNA Repair / drug effects
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DNA Repair Enzymes / drug effects
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Drug Resistance, Neoplasm*
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Flavonoids / therapeutic use
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Garlic / chemistry
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Glioblastoma / drug therapy*
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Humans
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Hypoxia-Inducible Factor 1, alpha Subunit / antagonists & inhibitors
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MicroRNAs / therapeutic use
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Neoplastic Stem Cells / pathology
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Proto-Oncogene Proteins c-bcl-2 / drug effects
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RNA, Small Interfering / therapeutic use
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Retinoids / therapeutic use
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Sulfides / therapeutic use
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Tumor Suppressor Proteins / drug effects
Substances
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ATP Binding Cassette Transporter, Subfamily B, Member 1
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ATP-Binding Cassette Transporters
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Allyl Compounds
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Angiogenesis Inhibitors
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Flavonoids
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Hypoxia-Inducible Factor 1, alpha Subunit
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MicroRNAs
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Proto-Oncogene Proteins c-bcl-2
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RNA, Small Interfering
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Retinoids
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Sulfides
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Tumor Suppressor Proteins
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allyl sulfide
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DNA Modification Methylases
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MGMT protein, human
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DNA Repair Enzymes