2019 Fiscal Year Final Research Report
Focusing on the Hsp72-binding molecule to overcome anticancer drug resistance in triple-negative breast cancer
| Project/Area Number |
17K15518
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Medical pharmacy
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| Research Institution | Osaka City University |
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Principal Investigator |
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| Project Period (FY) |
2017-04-01 – 2020-03-31
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| Keywords | 抗がん剤耐性 / トリプルネガティブ乳がん / 分子シャペロン |
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| Outline of Final Research Achievements |
Heat shock protein 72 (Hsp72) is a molecular chaperone that assists in the folding of nascent polypeptides and in the refolding of denatured proteins. In many cancers, Hsp72 is enhanced stabilizing oncogenic genes and stress tolerance.
We hypothesized that Hsp72 client proteins may play a crucial role in drug resistance. Human breast cancer cell lines MDA-MB-231 and 5-FU-resistant MDA-MB-231/5-FU was used. Anti-Hsp72 antibody was used to purify Hsp72-binding proteins and identified by LC/MS/MS. The identified proteins are molecules that affect the sensitivity of 5-FU and may be potential drug targets.
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| Free Research Field |
腫瘍薬学
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| Academic Significance and Societal Importance of the Research Achievements |
抗癌剤治療は完治を目的とするもの、生活の質を向上させる、すなわちCareを目的とするものがあり、特に後者では長期間、奏功する抗癌剤を使用する。長期投与となることから副作用の少ない5-FUのような薬剤が望ましい。耐性の獲得、副作用の出現は生存期間を短縮するだけでなく、生活の質を著しく損なう。トリプルネガティブ乳がんの薬物治療の選択肢は殺細胞性抗癌剤のみであり、本研究の目的である奏功していた薬剤を再び使用できる耐性を解除する標的分子の探索は意義深く、癌研究・医療に多大な貢献をもたらすことが期待できる。
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