| Budget Amount *help |
¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000)
Fiscal Year 2021: ¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2020: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2019: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2018: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
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| Outline of Final Research Achievements |
In this study, we revealed that ATR plays an important role in DNA replication stress tolerance and the acquisition of malignant phenotype by mutant KRASG12V in lung epithelial cells. In the presence of increased ATR expression, the slowed replication fork progression under KRASG12V-induced acute and chronic RS is unrestrained by an ATR kinase-dependent regulation of DNA replication stress tolerance candidate factors, which function as regulatory modules in the replication fork and complete replication. These mechanisms support cell survival but at the same time promote genomic instability leading to cell malignancy. These findings hold promise for the development of novel therapies using ATR inhibitors for patients with mutant KRAS lung cancer.
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