Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2019: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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Outline of Final Research Achievements |
PBIT, a small molecule inhibitor of the JARID1a/b histone demethylases, restored the drug sensitivity of multiple drug-resistant persister cells that were established from NSCLC lines. In addition, PBIT prevented the expansion of EGFR-TKI-resistant persisters through modifying secretomes from EGFR-TKI sensitive cells by inhibiting downregulation of FRA1 expression via prevention of decreased H3K4me3 levels at FRA1 promoter regions. These findings suggest the potential efficacy of PBIT as a novel therapeutic strategy for lung cancer and have particularly important implications in restoring drug resistance in NSCLC, given that patients with activating EGFR mutations who are given EGFR-targeted therapies commonly develop resistance.
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