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 |
Section | 一般 |
Review Section |
Basic Section 50020:Tumor diagnostics and therapeutics-related
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Research Institution | Keio University |
Principal Investigator |
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Project Period (FY) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2020: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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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 / がん分子標的治療薬 / がん分子標的薬 / AKT / シグナル伝達 |
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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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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Report
(4 results)
Research Products
(71 results)
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[Journal Article] SERCA and P-glycoprotein inhibition and ATP depletion are necessary for celastrol-induced autophagic cell death and collateral sensitivity in multidrug-resistant tumor cells.2020
Author(s)
Xu SW, Law BYK, Qu SLQ, Hamdoun S, Chen J, Zhang W, Guo JR, Wu AG, Mok SWF, Zhang DW, Xia C, Sugimoto Y, Efferth T, Liu L, Wong VKW.
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Journal Title
Pharmacological Research
Volume: 153
Pages: 104660-104660
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cytotoxicity of cucurbitacin E from Citrullus colocynthis against multidrug-resistant cancer cells.2019
Author(s)
Saeed MEM, Boulos JC, Elhaboub G, Rigano D, Saab A, Loizzo MR, Hassan LEA, Sugimoto Y, Piacente S, Tundis R, Yagi S, Khalid H, Efferth T.
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Journal Title
Phytomedicine
Volume: 62
Pages: 152945-152945
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Cytotoxicity of 40 Egyptian plant extracts targeting mechanisms of drug-resistant cancer cells.2019
Author(s)
Hegazy MF, Abdelfatah S, Hamed AR, Mohamed TA, Elshamy AA, Saleh IA, Reda EH, Abdel-Azim NS, Shams KA, Sakr M, Sugimoto Y, Pare PW, Efferth T.
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Journal Title
Phytomedicine
Volume: 59
Pages: 152771-152771
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] CAGE transcriptome analysis reveals BCL2A1 upregulation in FLT3-ITD/D835 dual mutated AML cells harboring complex co-mutations.2019
Author(s)
Yamatani K, Ai T, Saitoh K, Yang H, Suzuki K, Hori A, Murakami-Tonami, Y, Zhang W, Carter B, Kinjo S, Ikeo K, Katayama K, Sugimoto Y, Harada H, Miida T, Shah NP, Konopleva M, Hayashizaki Y, Andreeff M, Yoko Y.
Organizer
61st ASH Annual Meeting
Related Report
Int'l Joint Research
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