2021 Fiscal Year Final Research Report
Phenotype classification of high grade neuroendocrine lung cancer and development of novel molecular target therapy
| Project/Area Number |
19K18215
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 55040:Respiratory surgery-related
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| Research Institution | Tottori University |
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Principal Investigator |
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| Project Period (FY) |
2019-04-01 – 2022-03-31
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| Keywords | 小細胞肺癌 / Lurbinectedin / POU2F3 |
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| Outline of Final Research Achievements |
Small cell lung cancer (SCLC) is a progressive disease with a poor prognosis. Recently, a method to classify SCLC by the expression status of four transcriptional factors, ASCL1, NEUROD1, POU2F3, and YAP1, was proposed. We investigated the potential relationships between expression of these four transcription factors and the effect of lurbinectedin. Based on the results of qRT-PCR and western blot analyses, the eight SCLC cell lines examined were classified into NEUROD1, POU2F3, and YAP1 subtypes, as well as five ASCL1 subtypes. We found that the higher the mRNA expression level of POU2F3, the lower the IC50 of lurbinectedin. Evaluation of resected SCLC tissue revealed that the composition of subtypes defined by the relative dominance of ASCL1, NEUROD1, POU2F3, and YAP1 was as follows: 61% ASCL1, 15% NEUROD1, 14% POU2F3, 5% YAP1, and 5% all-negative. In our experiments, high mRNA expression of POU2F3 in SCLC cell lines correlated with the effect of lurbinectedin
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| Free Research Field |
呼吸器外科
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| Academic Significance and Societal Importance of the Research Achievements |
小細胞肺癌は難治がんの代表で、外科切除が出来た症例でも早期に再発を来すことが多い。根治には薬物療法が必須だが、効果が得られる薬剤は少なく、予後不良の原因となっている。近年、新規薬剤による治療開発が少しずつ進んでいるが、薬剤の効果が予測できるバイオマーカーは少ない。本研究では、小細胞肺癌細胞株における転写因子のPOU2F3発現が、新規薬剤のLurbinectedinの効果と有意な相関関係を認め、このPOU2F3がLurbinectedinの効果予測バイオマーカーとなる可能性が示唆された。治療薬の選択肢が少ない小細胞肺癌で、個別化医療を推進する発見の一つであり、本研究は一定の学術的意義を有する。
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