| 研究実績の概要 |
High-grade chondrosarcomas are chemo- and radio-resistant cartilage-forming tumors of bone that often relapse and metastase. Thus, new therapeutic strategies are urgently needed.
Chondrosarcoma cells (CH-2879) were exposed to carbon-ion irradiation, combined with miR-34 mimic and/or rapamycin administration. The effects of treatment on cancer stem cells, stemness-associated phenotype, radioresistance and tumor-initiating properties were evaluated.
We show that high-grade chondrosarcoma cells contain a population of radioresistant cancer stem cells that can be targeted by a combination of carbon-ion therapy, miR-34 mimic administration and/or rapamycin treatment that triggers FOXO3 and miR-34 over-expression. mTOR inhibition by rapamycin triggered FOXO3 and miR-34, leading to KLF4 repression.
Our results show that particle therapy combined with molecular treatments effectively controls cancer stem cells and may overcome treatment resistance of high-grade chondrosarcoma.
Vares, G., Ahire, V., Sunada, S., Kim, E. H., Sai, S., Chevalier, F., Romeo, PH, Yamamoto, T, Nakajima, T & Saintigny, Y. (2020). A multimodal treatment of carbon ions irradiation, miRNA-34 and mTOR inhibitor specifically control high-grade chondrosarcoma cancer stem cells. Radiotherapy and Oncology, 150, 253-261.
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| 現在までの達成度 (区分) |
現在までの達成度 (区分)
4: 遅れている
理由
I relocated to the Institute for Radioprotection and Nuclear Safety (IRSN) in France. Because this research project requires irradiation beam time at the HIMAC facility in QST, Chiba, we have been waiting for international borders to reopen and for international collaboration work to be authorized again after the COVID crisis. For this reason, no additional irradiation experiment could be carried out during the last fiscal year.
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