Analysis of the drug persistent cells to understand the acquired resistance mechanisms in lung cancer
| Project/Area Number |
19H03524
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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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 | Japanese Foundation for Cancer Research |
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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) |
2019-04-01 – 2022-03-31
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| Project Status |
Completed (Fiscal Year 2021)
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| Budget Amount *help |
¥17,420,000 (Direct Cost: ¥13,400,000、Indirect Cost: ¥4,020,000)
Fiscal Year 2021: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2020: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000)
Fiscal Year 2019: ¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
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| Keywords | 薬剤耐性 / 分子標的薬 / 治療残存細胞 / 肺がん / 残存腫瘍 |
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| Outline of Research at the Start |
進行肺がんの予後は約15年前までは非常に短く1年程度しかなかったが、近年の各種薬物療法の目覚ましい進歩により、著しい改善がみられてきた。しかし、獲得耐性の出現が今なお大きな問題として立ちはだかっている。本研究では、いつ、どのように、耐性は生じていき、なぜ現状獲得耐性が避けられないのかということを、治療薬奏功後にわずかに残る治療残存細胞に注目した形で研究を進め、新規治療標的となる分子や新規治療法を同定し、「耐性を生じなく（生じにくく）する新しい治療法」の発見を目指す。
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| Outline of Final Research Achievements |
Recently, development of molecular-targeted drugs and cancer immunotherapy remarkably improved the prognosis of advanced lung cancer, but the emergence of acquired resistance and primary resistance in a certain fraction of patients are major obstacles to further improve cancer therapy. In this study, we investigated when and how drug resistant cancer emerges, by focusing on the drug tolerant persister cells that could be a seed of drug-resistance, and explored therapeutic target molecules, pathways, and therapeutic strategies. We discovered that GSK3 could be a potential target in drug tolerant persister cells in ALK-rearranged lung cancer. In addition, we successfully found and published a new effective drug candidate for multidrug-resistant ALK-TKI resistant compound mutations.
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| Academic Significance and Societal Importance of the Research Achievements |
進行がんの治療は目覚ましく進歩しているが、耐性出現が免れられないため、治療時にもわずかに残る細胞の性状解析から耐性細胞出現を抑制したり遅くしたりすることが期待できる。本研究で見出した治療残存細胞の新たな治療標的候補発見はこれまでに報告の無い新たな因子の関与を見出したものであり学術的意義は高い。なお、本研究で見出した多剤耐性変異型ALKにも有効な治療法候補の発見は、他のがんを対象とした既存薬による治療応用の可能性についての研究であり、臨床応用へとつなげることができると学術的および社会的意義の高い研究となることが期待できる。
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Report
(4 results)
Research Products
(46 results)
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[Journal Article] HER3 activation contributes toward the emergence of ALK inhibitor-tolerant cells in ALK-rearranged lung cancer with mesenchymal features.2022
Author(s)
Tanimura K, Yamada T, Okada K, Nakai K, Horinaka M, Katayama Y, Morimoto K, Ogura Y, Takeda T, Shiotsu S, Ichikawa K, Watanabe S, Morimoto Y, Iwasaku M, Kaneko Y, Uchino J, Taniguchi H, Yoneda K, Matoba S, Sakai T, Uehara H, Yano S, Kusaba T, Katayama R, Takayama K.
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Journal Title
NPJ Precis Oncol.
Volume: 6
Issue: 1
Pages: 5-5
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Gilteritinib overcomes lorlatinib resistance in ALK-rearranged cancer2021
Author(s)
Mizuta Hayato、Okada Koutaroh、Araki Mitsugu、Adachi Jun、Takemoto Ai、Kutkowska Justyna、Maruyama Kohei、Friboulet Luc、Katayama Kazuhiro、Ma Biao、Sasakura Yoko、Sagae Yukari、Kukimoto-Niino Mutsuko、Shirouzu Mikako、Takagi Satoshi、Simizu Siro、Nishio Makoto、Okuno Yasushi、Fujita Naoya、Katayama Ryohei, et al
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 1261-1261
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Osimertinib Overcomes Alectinib Resistance Caused by Amphiregulin in a Leptomeningeal Carcinomatosis Model of ALK-Rearranged Lung Cancer.2020
Author(s)
Sachiko Arai, Shinji Takeuchi, Koji Fukuda, Hirokazu Taniguchi, Akihiro Nishiyama, Azusa Tanimoto, Miyako Satouchi, Kaname Yamashita, Koshiro Ohtsubo, Shigeki Nanjo, Toru Kumagai, Ryohei Katayama, Makoto Nishio, Mei-Mei Zheng, Yi-Long Wu, Hiroshi Nishihara, Takushi Yamamoto, Mitsutoshi Nakada, Seiji Yano
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Journal Title
Journal of thoracic oncology
Volume: 15
Issue: 5
Pages: 752-765
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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