Molecular targeted medicine to inhibit cancer stemness
Project/Area Number |
26293196
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Respiratory organ internal medicine
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Research Institution | Saitama Medical University (2015-2016) Niigata University (2014) |
Principal Investigator |
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Co-Investigator(Kenkyū-buntansha) |
矢野 聖二 金沢大学, がん進展制御研究所, 教授 (30294672)
梅津 哉 新潟大学, 医歯学総合病院, 准教授 (50251799)
土田 正則 新潟大学, 医歯学系, 教授 (60293221)
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Project Period (FY) |
2014-04-01 – 2017-03-31
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Project Status |
Completed (Fiscal Year 2016)
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Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000)
Fiscal Year 2015: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000)
Fiscal Year 2014: ¥7,930,000 (Direct Cost: ¥6,100,000、Indirect Cost: ¥1,830,000)
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Keywords | DDX3X / Wnt/β-catenin / VEGF / EGFR遺伝子変異陽性肺癌 / PD-1 / EGFR / 肺癌 / beta-catenin / VEGFR / β-catenin / 癌幹細胞 |
Outline of Final Research Achievements |
EGFR-TKI has led to unprecedented results in lung cancer patients harboring activating EGFR mutations. However, the phenotypic diversity of cancer cells results in the survival of treatment-resistant cells. DDX3X is a RNA helicase and is involved in Wnt/β-catenin signal activation. We identified lung cancer cells that expressed DDX3X achieve cancer stem cell-like and mesenchymal properties resulting in EGFR-TKI resistance. Response rate of DDX3X positive EGFR mutant lung cancer patients was only 13.3 %. In this study, we demonstrated that Wnt/β-catenin or VEGFR signal inhibitors exhibited synergistic antitumor reactivity to break EGFR-TKI resistance. Clinical sample analyses revealed that DDX3X expression was accompanied withβ-catenin and VEGFR-2 expression. Our data indicate a novel mechanism how lung cancer cells harboring EGFR-activating mutations survive through EGFR-TKI treatment and have a clinical implication to develop a novel treatment for VEGFR- and β-catenin-signaling.
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Report
(4 results)
Research Products
(19 results)
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[Journal Article] Megalin Blockade with Cilastatin Suppresses Drug-Induced Nephrotoxicity.2017
Author(s)
Hori Y, Aoki N, Kuwahara S, Hosojima M, Kaseda R, Goto S, Iida T, De S, Kabasawa H, Kaneko R, Aoki H, Tanabe Y, Kagamu H, Narita I, Kikuchi T, Saito A.
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Journal Title
J Am Soc Nephrol.
Volume: January 4
Issue: 2
Pages: 227-234
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] A phase II study of bevacizumab with carboplatin-pemetrexed in non-squamous non-small cell lung carcinoma patients with malignant pleural effusions: North East Japan Study Group Trial NEJ013A.2016
Author(s)
Usui K, Sugawara S, Nishitsuji M, Fujita Y, Inoue A, Mouri A, Watanabe H, Sakai H, Kinoshita I, Ohhara Y, Maemondo M, Kagamu H, Hagiwara K, Kobayashi K
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Journal Title
Lung Cancer
Volume: 99
Pages: 131-136
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Anamorelin (ONO-7643) in Japanese patients with non-small cell lung cancer and cachexia: results of a randomized phase 2 trial.2016
Author(s)
Takayama, K., Katakami, N., Yokoyama, T., Atagi, S., Yoshimori, K., Kagamu, H., Saito, H., Takiguchi, Y., Aoe, K., Koyama, A., Komura, N. and Eguchi, K
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Journal Title
Supportive care in cancer
Volume: NA
Issue: 8
Pages: 1-11
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] Nephrotoxicity of cisplatin combination chemotherapy in thoracic malignancy patients with CKD risk factors.2016
Author(s)
Ko Sato, Satoshi Watanabe,corresponding author Aya Ohtsubo, Satoshi Shoji, Daisuke Ishikawa, Tomohiro Tanaka, Koichiro Nozaki, Rie Kondo, Masaaki Okajima, Satoru Miura, Junta Tanaka, Takuro Sakagami, Toshiyuki Koya, Hiroshi Kagamu, Hirohisa Yoshizawa, and Ichiei Narita
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Journal Title
BMC Cancer
Volume: 16(1)
Issue: 1
Pages: 222-222
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Critical Roles of Chemoresistant Effector and Regulatory T Cells in Antitumor Immunity after Lymphodepleting Chemotherapy.2015
Author(s)
Saida Y, Watanabe S, Tanaka T, Baba J, Sato K, Shoji S, Igarashi N, Kondo R, Okajima M, Koshio J, Ichikawa K, Nozaki K, Ishikawa D, Koya T, Miura S, Tanaka J, Kagamu H, Yoshizawa H, Nakata K, Narita I
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Journal Title
Journal of immunology
Volume: 195(2)
Issue: 2
Pages: 726-735
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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[Presentation] DDX3X induces signal switching to stem cell-specific Wnt/β-catenin signaling, resulting in EGFR-TKI resistance in lung cancer cells harboring EGFR activating mutation2014
Author(s)
Satoshi Shoji, Hiroshi Kagamu, Koichiro Nozaki, Natsue Igarashi, Masaaki Okajima, Satoru Miura, Satoshi Watanabe, Hirohisa Yoshizawa, and Ichiei Narita
Organizer
American Association for Caner Research annual meeting
Place of Presentation
San Diego Convention Center(San Diego, USA)
Year and Date
2014-04-05 – 2014-04-09
Related Report
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