Abstract
Progress in stem cell research has been associated with the discovery of the presence of cancer stem cells in a variety of malignant tumors, and because these cells are resistant to anticancer agents and radiotherapy, analysis of their properties has been rapidly pursued as an important target for the treatment of cancers, including malignant brain tumors. Brain cancer stem cells (BCSCs) have been isolated from brain tumor tissue and brain tumor cell lines by using neural stem cell culture methods. Analyzing the properties of BCSCs is extremely important to developing treatment methods that target BCSCs. Although no treatment method targeting BCSCs has yet been established, several methods have been proposed based on their cell-biological characteristics. This article describes therapeutic strategies that target drug-resistance molecules and stem-cell-associated molecules as well as immunotherapy targeted at BCSCs.
Highlights
Progress in stem cell research has been associated with the discovery of the presence of cancer stem cells in a variety of malignant tumors, and because these cells are resistant to anticancer agents and radiotherapy, analysis of their properties has been rapidly pursued as an important target for the treatment of cancers, including malignant brain tumors
After the existence of cancer stem cells was demonstrated, and because cancer stem cells are proficient at DNA repair and exhibit high gene expression levels of ATP-binding cassette half-transporter proteins (ABC transporters), the following new hypothesis was proposed: cancer stem cells are resistant to anticancer agents, and they persist after chemotherapy and become the source of tumor regrowth [1]
An attempt to eliminate Brain cancer stem cells (BCSCs) with bone morphogenetic protein (BMP), a molecule that induces the differentiation of neural stem cells (NSCs) into astrocytes, has been reported [10]
Summary
Genetic mutations in the target molecules of drugs, expression of molecules that inactivate drugs, and mechanisms that excrete drugs from cells have all been identified as ways that cancer cells acquire resistance to chemotherapeutic agents [1]. Inhibitors of ABC transporters, which are drug resistance molecules, have attracted interest as candidate therapeutic agents for use against cancer stem cells. Because of the high levels of ABCG2 and ABCG5 expression in cancer stem cells, inhibitors and antibodies to these molecules are being considered as candidate therapeutic agents. Since BMP4 exhibits an antitumor effect against transplanted tumors in vivo, the development of methods for targeting BCSCs with molecules that induce stem cell differentiation has attracted much interest. Vascular endothelial growth factor (VEGF), an endothelial growth factor, has been shown to control the BCSC microenvironment, and because VEGF antibodies have already been applied clinically, VEGF antibodies are expected to serve as a therapeutic agent against BCSCs. Immunotherapy consists of active immunotherapy, which induces and strengthens antitumor immunity in cancer patients’ own bodies by vaccinating patients with tumor cells. Immunotherapy with BCSCs themselves, rather than with tumor antigens, may be a feasible method of treating brain tumors
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