2020 Fiscal Year Final Research Report
Analysis of the resistance mechanisms to molecular-targeting anticancer agents
| Project/Area Number |
18K07302
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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| Research Institution | Keio University |
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Principal Investigator |
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| Project Period (FY) |
2018-04-01 – 2021-03-31
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| Keywords | がん分子標的治療 / 薬剤耐性 / がん幹細胞 / トランスポーター |
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| Outline of Final Research Achievements |
Upregulation of AKT3 was found in PLK inhibitor-resistant cells and AURK inhibitor-resistant cells. AKT3 lowered the frequency of multipolar spindle formation in mitotic cells. Upregulation of TNIK was found in BET inhibitor-resistant cells. TNIK was found to be involved in cell cycle control and drug resistance. 116/slug cells are SLUG-induced EMT cells with mesenchymal morphology and contain side population (SP) cells. BET inhibitors diminished the SP cells of 116/slug. 116/slug cells showed high sensitivity to GPX4 inhibitors. MINPP1 was shown to regulate the expression of multidrug efflux transporter P-glycoprotein.
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| Free Research Field |
がん化学療法
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| Academic Significance and Societal Importance of the Research Achievements |
近年、がん細胞の生存と増殖を制御する種々の分子に対する阻害薬が開発され、がん治療への応用が試みられている。本研究では、PLK阻害薬、AURK阻害薬、BET阻害薬およびその耐性細胞を用いて、これらの阻害薬の作用機構およびがん細胞の阻害薬耐性・感受性を決定する因子を明らかにした。また、上皮間葉転換、がん幹細胞、薬物排出トランスポーターの関与する阻害薬耐性・感受性についても新しい知見を得た。こうした研究を積み重ねることにより、がんに対してより有効な薬物療法が構築できると考えている。
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