2021 Fiscal Year Research-status Report
Combination therapies for chondrosarcoma
| Project/Area Number |
19K07765
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| Research Institution | Okinawa Institute of Science and Technology Graduate University |
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Principal Investigator |
Guillaume Vares 沖縄科学技術大学院大学, 細胞シグナルユニット, 客員研究員 (10415432)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | chondrosarcoma / particle therapy / radiotherapy / cancer stem cells / cancer / micro-RNA |
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| Outline of Annual Research Achievements |
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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| Current Status of Research Progress |
Current Status of Research Progress
4: Progress in research has been delayed.
Reason
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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| Strategy for Future Research Activity |
We plan to characterize molecular pathways associated with combination therapies in normoxia and physioxia. Additional experiments will require access to a particle radiation facility (HIMAC or another facility if borders do not reopen soon).
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