| Item type |
文献 / Documents(1) |
| 公開日 |
2024-12-09 |
| アクセス権 |
|
|
アクセス権 |
open access |
|
アクセス権URI |
http://purl.org/coar/access_right/c_abf2 |
| 資源タイプ |
|
|
資源タイプ識別子 |
http://purl.org/coar/resource_type/c_db06 |
|
資源タイプ |
doctoral thesis |
| 出版社版DOI |
|
|
|
関連識別子 |
https://doi.org/10.1002/prp2.1214 |
|
|
関連名称 |
10.1002/prp2.1214 |
| 出版タイプ |
|
|
出版タイプ |
NA |
|
出版タイプResource |
http://purl.org/coar/version/c_be7fb7dd8ff6fe43 |
| タイトル |
|
|
タイトル |
Asciminib, a novel allosteric inhibitor of BCR-ABL1, shows synergistic effects when used in combination with imatinib with or without drug resistance |
| タイトル別表記 |
|
|
その他のタイトル |
新規BCR-ABL1 アロステリック阻害剤アシミニブは薬剤耐性の有無に関わらずイマチニブとの併用で相乗効果を示す |
| 著者 |
岡本, 尚大
八木, 健太
Imawaka, Sayaka
Takaoka, Mayu
相澤, 風花
新村, 貴博
合田, 光寛
Miyata, Koji
川田, 敬
(井澤)石澤, 有紀
坂口, 暁
石澤, 啓介
|
| 抄録 |
|
|
内容記述 |
In the treatment of chronic myeloid leukemia (CML), resistance to BCR-ABL inhibitors makes it difficult to continue treatment and is directly related to life expectancy. Therefore, asciminib was introduced to the market as a useful drug for overcoming drug resistance. While combining molecular targeted drugs is useful to avoid drug resistance, the new BCR-ABL inhibitor asciminib and conventional BCR-ABL inhibitors should be used as monotherapy in principle. Therefore, we investigated the synergistic effect and mechanism of the combination of asciminib and imatinib. We generated imatinib-resistant cells using the human CML cell line K562, examined the effects of imatinib and asciminib exposure on cell survival using the WST-8 assay, and comprehensively analyzed genetic variation related to drug resistance using RNA-seq and real-time PCR. A synergistic effect was observed when imatinib and asciminib were combined with or without imatinib resistance. Three genes, GRRP1, ESPN, and NOXA1, were extracted as the sites of action of asciminib. Asciminib in combination with BCR-ABL inhibitors may improve the therapeutic efficacy of conventional BCR-ABL inhibitors and prevent the development of resistance. Its dosage may be effective even at minimal doses that do not cause side effects. Further verification of this mechanism of action is needed. Additionally, cross-resistance between BCR-ABL inhibitors and asciminib may occur, which needs to be clarified through further validation as soon as possible. |
| キーワード |
|
|
主題 |
CML |
| キーワード |
|
|
主題 |
chronic myelogenous leukemia |
| キーワード |
|
|
主題 |
Asciminib |
| キーワード |
|
|
主題 |
BCR-ABL inhibitors |
| キーワード |
|
|
主題 |
Drug Resistance |
| 書誌情報 |
en : Pharmacology Research & Perspectives
巻 12,
号 4,
p. e1214,
発行日 2024-06-21
|
| 収録物ID |
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|
収録物識別子タイプ |
EISSN |
|
収録物識別子 |
20521707 |
| 出版者 |
|
|
出版者 |
British Pharmacological Society |
| 出版者 |
|
|
出版者 |
American Society for Pharmacology and Experimental Therapeutics |
| 出版者 |
|
|
出版者 |
John Wiley & Sons |
| 備考 |
|
|
値 |
内容要旨・審査要旨・論文本文の公開
本論文は，著者Naoki Okamotoの学位論文として提出され，学位審査・授与の対象となっている。
学位授与者所属 : 徳島大学大学院医学研究科（医学専攻） |
| 権利情報 |
|
|
権利情報 |
This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| EID |
|
|
識別子 |
415119 |
| 言語 |
|
|
言語 |
eng |
| 報告番号 |
|
|
学位授与番号 |
甲第3845号 |
| 学位記番号 |
|
|
値 |
甲医第1616号 |
| 学位授与年月日 |
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|
学位授与年月日 |
2024-09-12 |
| 学位名 |
|
|
学位名 |
博士（医学） |
| 学位授与機関 |
|
|
|
学位授与機関名 |
徳島大学 |
k3845_abstract.pdf (125 KB)
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