| Budget Amount *help |
¥16,250,000 (Direct Cost: ¥12,500,000、Indirect Cost: ¥3,750,000)
Fiscal Year 2021: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2020: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000)
Fiscal Year 2019: ¥6,890,000 (Direct Cost: ¥5,300,000、Indirect Cost: ¥1,590,000)
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| Outline of Final Research Achievements |
Cancer cells exposed to targeted drugs emerge tolerant cells that allow some to survive as resistant cells and later proliferate. In this study, we found that EGFR-mutated lung cancer cells with low AXL expression emerge tolerant cells to the EGFR inhibitor osimertinib by increasing the expression of the transcription factor FOXA1 to activate IGF-1R. We further found that TP53 mutation and STAT3 activation induce apoptosis resistance to ALK inhibitors and cause ALK inhibitor tolerance in ALK rearranged lung cancer cells. In addition, combined use of proteasome inhibitors or STAT3 inhibitors could augment the efficacy of ALK inhibitors against ALK rearranged lung cancer cells.
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