Cancer stem cells: The potential of carbon ion beam radiation and new radiosensitizers (Review)

Abstract

Abstract. Cancer stem cells (CSCs) are a small population of cells in cancer with stem-like properties such as cell proliferation, multiple differentiation and tumor initiation capacities. CSCs are therapy-resistant and cause cancer metastasis and recurrence. One key issue in cancer therapy is how to target and eliminate CSCs, in order to cure cancer completely without relapse and metastasis. To target CSCs, many cell surface markers, DNAs and microRNAs are considered as CSC markers. To date, the majority of the reported markers are not very specific to CSCs and are also present in nonCSCs. However, the combination of several markers is quite valuable for identifying and targeting CSCs, although more specific identification methods are needed. While CSCs are considered as critical therapeutic targets, useful treatment methods remain to be established. Epigenetic gene regulators, microRNAs, are associated with tumor initiation and progression. MicroRNAs have been recently considered as promising therapeutic targets, which can alter the therapeutic resistance of CSCs through epigenetic modification. Moreover, carbon ion beam radiotherapy is a promising treatment for CSCs. Evidence indicates that the carbon ion beam is more effective against CSCs than the conventional X-ray beam. Combination therapies of radiosensitizing microRNAs and carbon ion beam radiotherapy may be a promising cancer strategy. This review focuses on the identification and treatment resistance of CSCs and the potential of microRNAs as new radiosensitizers and carbon ion beam radiotherapy as a promising therapeutic strategy against CSCs.

Carbon ion beam radioresistant rodent cells are sensitized to trifluorothymidine exposure

“…Carbon ion beam radiotherapy resistance mechanisms are not fully understood. Although the anticancer mechanism of X-ray radiation (ROS production) facilitates the survival of cancer stem cells, the unique mechanisms involved in the process of cancer cell survival are not mutually exclusive (4). In the present study, an X-ray-resistant cell line (X60) and a carbon ion beam-resistant cell line (C30) were studied using mice.…”

“…Whereas a systemic review indicated that the mechanism by which ionized radiation therapy may induce apoptosis of cancer cells involves redox regulation (2), one study revealed that X-rays induced the production of reactive oxygen species (ROS), and that cancer stem cells and other small fractions of tumor tissues were able to survive following therapy (3). By contrast, carbon ion beam radiotherapy typically exerts antitumor effects directly on cellular organelles, including the nucleus, in which the DNA may be exposed to double-stranded breaks (4). As DNA double-stranded breaks are harmful to cells, this presents a promising therapeutic mechanism via which efficient eradication of tumors is expected (5).…”

“…Evaluation of optimal chemotherapy regimens is important for improving treatment outcomes, as it serves an important function in eliminating metastases and microinvasions, which may cause tumor recurrence (4). For X-ray radioresistance, clinical trials have examined a number of drugs and treatments in order to determine the most effective combination and types; for example, cisplatin (CDDP) and 5-fluorouracil (5-FU) are typically used in combination with X-ray radiotherapy (2)(3)(4). A previous study demonstrated that a combination of trifluorothymidine (FTD) and the thymidine phosphorylase inhibitor, tipiracil HCl (TAS-102), was effective against 5-FU-resistant cancer (9).…”

MicroRNA miR-374, a potential radiosensitizer for carbon ion beam radiotherapy

“…Although clinical and pathological studies have shown that the mechanism by which densely ionizing radiation induces apoptosis in cancer cells involves redox regulation (2), a study has revealed that cancer stem cells and minor fractions of other cancer cells are able to survive radiation therapy (3). In contrast, charged particle therapy is generally supposed to exert its antitumor effects directly on cellular DNA, which is vulnerable to double-strand breaks (4). Because DNA double-strand breaks are lethal to cells (5), this may be a promising therapeutic mechanism for efficient eradication of cancer cells.…”

“…A growing body of evidence has suggested that small non-coding RNAs, known as microRNAs (miRNAs), are involved in the regulation of tumor initiation and progression (4,(6)(7)(8)(9). Several miRNAs have been found to be prognostic factors and clinical targets for cancer treatment (9-13).…”