| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Outline of Final Research Achievements |
On the basis of our proposal that inhibition of S phase causes cancer cells to proceed into lethal M phase in the presence of unreplicated genomic segment, we proposed a novel cancer therapy strategy in which cancer cell death is promoted by combination of S phase inhibition and M phase promotion. We used inhibitors of Cdc7 kinase, essential for firing of replication origins in S phases, and showed that the Cdc7 inhibitor causes cell death only after cells have progressed through S phase in the presence of the inhibitor, apparently causing cancer cells to enter aberrant M phase. When combined with MK1775, the inhibitor of Wee1 kinase that inhibits M phase, Cdc7 inhibitor caused synergistic cell death effect on cancer cells including Colo205 (colon cancer) and CCRF-CEM(leukemia). HU and Aphidicolin also induced efficient cancer cell death in combination with MK1775.
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