| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
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| Outline of Final Research Achievements |
Novel therapies for refractory osteosarcoma (OS) must be developed. We focused on metabolism and performed metabolome analyses using our unique mouse model. Glycolysis and protein synthesis were upregulated in metastatic cells. Consistent with this, cytarabine exhibited a potent antitumor effect. Based on metabolite levels, non-adherent conditions were more similar to the in vivo environment than adherent conditions. A drug screen identified trametinib that preferentially decreased the viability of non-adherent cells. Notably, activation status of several kinases and crosstalk between MEK-ERK and PI3K-AKT pathways varied in OS, that might determine the response to MEK inhibition. A single dose of trametinib decreased primary tumors and CTCs. Moreover, combined administration of trametinib and anticancer drugs was effective for metastasis.
Thus, combination of trametinib and agents targeting metabolism such as cytarabine holds therapeutic potential for treatment of OS.
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