2020 Fiscal Year Final Research Report
Development of curative treatment for non-small cell lung cancer harboring ROS1 fusion gene.
Project/Area Number |
19K23916
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Research Category |
Grant-in-Aid for Research Activity Start-up
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Allocation Type | Multi-year Fund |
Review Section |
0901:Oncology and related fields
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Research Institution | Okayama University |
Principal Investigator |
Kato Yuka 岡山大学, 大学病院, 講師 (50544904)
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Project Period (FY) |
2019-08-30 – 2021-03-31
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Keywords | ROS1融合遺伝子 / クリゾチニブ / ロルラチニブ |
Outline of Final Research Achievements |
The cell lines ABC-26 (parental line) and ABC-20 (resistant line) were established from pleural fluid of ROS1 fusion gene-positive lung cancer patients before and 6 months after crizotinib (ROS1 inhibitor) treatment, respectively. Both ABC-20 and ABC-26 remained sensitive to lorlatinib, a second-generation ROS1 inhibitor (IC50; 0.039 μM), while ABC-20 was resistant to crizotinib (IC50; 0.767 μM). (IC50; 0.008 μM, 0.0002 μM), and the results of Western Blotting showed similar results. This suggests that lorlatinib is an effective drug both before and after crizotinib resistance. Based on these results, we validated the results using the Xenograft model, and found that lorlatinib had a strong tumor-reducing effect, although crizotinib did not have a tumor-reducing effect in the model using the resistant ABC-20 strain.
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Free Research Field |
肺癌
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Academic Significance and Societal Importance of the Research Achievements |
本研究の結果、第二世代ROS1阻害剤であるロルラチニブがクリゾチニブ耐性を克服し、強い腫瘍縮小効果を得ることが可能であることが示唆された。ROS1肺癌患者は、非喫煙で若年者に多く社会的にも重要な疾患群である。しかし、免疫チェックポイント阻害剤の効果も乏しいことが報告されており、治療方法が限定されていることから、治療戦略が非常に重要である。本研究結果から、初回治療に用いたクリゾチニブの効果が消失した後に、ロルラチニブを使用することでより強い腫瘍縮小効果が得られ、更には延命効果が期待されたことは社会的意義が非常に高いと考える。
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