2022 Fiscal Year Final Research Report
Identification of lncRNAs that influence BRAF mutation signal dependency
| Project/Area Number |
19K07740
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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 | Juntendo University |
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Principal Investigator |
Kato Shunsuke 順天堂大学, 大学院医学研究科, 教授 (40312657)
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| Co-Investigator(Kenkyū-buntansha) |
藤井 智明 順天堂大学, 医学部, 非常勤助教 (10511420)
山口 茂夫 順天堂大学, 医学部, 非常勤助教 (40747797)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Keywords | drug resistance / malanoma / BRAF / long non-coding RNA |
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| Outline of Final Research Achievements |
BRAF V600E mutation is a typical driver mutation in oncogenesis reported across different types of cancer, such as malignant melanoma, thyroid cancer, lung cancer, colorectal cancer etc. Molecular target drugs (BRAF inhibitors) that suppress the dysfunction of BRAF gene mutations have been developed for therapeutic purposes, but drug resistance has become a problem. In this study, we clarified that some non-coding RNAs are involved in the resistance mechanism against BRAF inhibitors. Non-coding RNA molecules are known to play a role in regulating the stability of intracellular proteins and RNA. Our data showed that the identified non-coding RNA regulate the RNA expression level of genes known to be involved in resistance mechanisms, such as the MITF gene.
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| Free Research Field |
臨床腫瘍学
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| Academic Significance and Societal Importance of the Research Achievements |
がん治療の現場では、遺伝子の変異に応じてその機能を制御する様々な分子標的薬剤の開発が進んでいるが、治療過程で薬剤に対する耐性が生じることが臨床的な問題となっている。BRAF阻害剤の耐性メカニズムの一因に非コーディングRNA分子が関わっていることを明らかにした今回の成果を応用し、腫瘍内の非コーディングRNA分子を定量化することで、治療効果予測が事前にでき、効果が期待できる患者に必要な治療を提供することが可能となるとともに、抵抗性が予測される患者には非コーディングRNAの制御療法を併用することで治療効果を上げることが期待できる。
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