2021 Fiscal Year Final Research Report
Molecular mechanisms of paradoxical growth suppression by over activation of oncogene kinases
Project/Area Number |
20K21554
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Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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Allocation Type | Multi-year Fund |
Review Section |
Medium-sized Section 50:Oncology and related fields
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Research Institution | Japanese Foundation for Cancer Research |
Principal Investigator |
KATAYAMA Ryohei 公益財団法人がん研究会, がん化学療法センター 基礎研究部, 部長 (60435542)
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Project Period (FY) |
2020-07-30 – 2022-03-31
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Keywords | キナーゼ / 過剰活性化 / 薬剤耐性 |
Outline of Final Research Achievements |
Various kinase inhibitors have been developed, and approved as molecular targeting drugs for cancer. However, in many cases, drug resistance inevitably occurs, and occasionally mutations that further increase kinase activity occurred. In such cases, we have found that the excess activation target kinase by temporally removing inhibitors inversely suppress cancer cell growth. In the present study, we tried to understand the mechanism of excessive kinase activity induced growth suppression to find new potential therapeutic targets. As a result, we found that several ALK-positive lung cancers that have developed resistance to therapy actually show excessive kinase activity, and also find that a certain factor plays an important role in that process.
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Free Research Field |
腫瘍学
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Academic Significance and Societal Importance of the Research Achievements |
キナーゼ阻害薬などの分子標的薬に対して耐性がん細胞が出現する際には、様々な変異や他のがん遺伝子の活性化などが生じる。この時薬剤が除去されると、もともとのドライバーがん遺伝子からのシグナルに加えて、耐性時に獲得したシグナルも加わり過剰な増殖シグナルとなる。このことががんの増殖にとって不利に働くことのメカニズムが本研究により少しずつ明らかになっており、また実際に患者検体からもこのような現象があることが判明しつつあることは、今後新たな治療戦略を見出す可能性につながり、学術的意義は高い。
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