Search of the effect predictive factor in molecules target therapy for lung cancer

• Project/Area Number: 24591156
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory organ internal medicine
• Research Institution: Niigata University
• Principal Investigator: YOSHIZAWA Hirohisa 新潟大学, 医歯学総合病院, 特任教授 (50282984)
• Co-Investigator(Kenkyū-buntansha): WATANABE Satoshi 新潟大学, 医歯学総合病院, 特任助教 (50529740) ; NAKATA Koh 新潟大学, 医歯学総合病院, 教授 (80207802)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2013: ¥1,040,000 (Direct Cost: ¥800,000、Indirect Cost: ¥240,000); Fiscal Year 2012: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: Lung cancer / EGFR-TKI / MDSCs / Predictive factor / Regulatory T細胞 / 制御性T細胞 / αGalCel

Outline of Final Research Achievements

Several immunologic parameters in patients with positive EGFR-mutation NSCLC during initial EGFR-TKI treatment were measured. The tendency that decreased frequency in the peripheral blood of the CD4+ CD25+ Foxp3+Regulatory T cell during tumor regression was found. In contrast, analysis of MDSCs or various humoral factors showed no particular tendency. During the series of experiments, we found that DDX3X expression and CD4+ CD25+ Foxp3+ Regulatory T cell affecting acquisition of resistancy to TKI.

Research Products

• [Journal Article] Factors associated with a poor response to gefitinib in the NEJ002 study: Smoking and the L858R mutation. (2015)
  • Author(s): Fukuhara T, Yoshizawa H et al.
  • Journal Title: Lung Cancer Volume: 88 Issue: 2 Pages: 181-6
  • DOI: 10.1016/j.lungcan.2015.02.004
  • Peer Reviewed / Open Access
• [Journal Article] DDX3X induces primary EGFR-TKI resistance based on intratumor heterogeneity in lung cancer cells harboring EGFR-activating mutations. (2014)
  • Author(s): Nozaki K, Yoshizawa H et al.
  • Journal Title: PLoS One Volume: 9 Issue: 10 Pages: e111019-e111019
  • DOI: 10.1371/journal.pone.0111019
  • Peer Reviewed / Open Access
• [Journal Article] Effectiveness of gefitinib against non-small-cell lung cancer with the uncommon EGFR mutations G719X and L861Q. (2014)
  • Author(s): Watanabe S, Yoshizawa H et al.
  • Journal Title: J Thorac Oncol. Volume: 11 Issue: 2 Pages: 189-94
  • DOI: 10.1097/jto.0000000000000048
  • Peer Reviewed / Open Access
• [Journal Article] The efficacy of triplet antiemetic therapy with 0.75 mg of palonosetron for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy. (2013)
  • Author(s): Miura S, Watanabe S, Sato K, Makino M, Kobayashi O, Miyao H, Iwashima A, Okajima M, Tanaka J, Tanaka H, Kagamu H, Yokoyama A, Narita I, Yoshizawa H.
  • Journal Title: Support Care Cancer Volume: 21 Issue: 9 Pages: 2575-2581
  • DOI: 10.1007/s00520-013-1835-2
  • Peer Reviewed
• [Journal Article] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked is an immunogenic target of cancer stem cells (2013)
  • Author(s): Koshio, J. Kagamu, H. Nozaki, K. Saida, Y. Tanaka, T. Shoji, S. Igarashi, N. Miura, S. Okajima, M. Watanabe, S. Yoshizawa, H. Narita, I.
  • Journal Title: Cancer Immunol Immunother Volume: 62 Issue: 10 Pages: 1619-28
  • DOI: 10.1007/s00262-013-1467-x
  • Peer Reviewed
• [Journal Article] mTOR inhibitors control erlotinib-resistance of EGFR mutant lung cancer cells triggered by HGF. (2013)
  • Author(s): Ishikawa D, Yano S, et al.
  • Journal Title: PLoS ONE Volume: 8 Issue: 5 Pages: e62104-e62104
  • DOI: 10.1371/journal.pone.0062104
  • Peer Reviewed
• [Journal Article] Updated Overall Survival Results from A Randomized Phase III Trial Comparing Gefitinib with Carboplatin-Paclitaxel for Chemo-Naive Non-Small Cell Lung Cancer with Sensitive EGFR Gene Mutations (NEJ002) (2013)
  • Author(s): Inoue A, Kobayashi K, Maemondo M, et al
  • Journal Title: Ann Oncol Volume: 24 Issue: 1 Pages: 54-9
  • DOI: 10.1093/annonc/mds214
  • Peer Reviewed
• [Journal Article] Depletion of radio-resistant regulatory T cells enhances antitumor immunity during recovery from lymphopenia (2012)
  • Author(s): Baba J, Watanabe S, Saida Y, Tanaka T, Miyabayashi T, Koshio J, Ichikawa K, Nozaki K, Koya T, Deguchi K, Tan C, Miura S, Tanaka H, Tanaka J, Kagamu H, Yoshizawa H, Nakata K, Narita I.
  • Journal Title: Blood Volume: 12 Pages: 2417-2427
  • Peer Reviewed
• [Journal Article] Epitope diversification driven by non-tumor epitope-specific Th1 and Th17 mediates potent antitumor reactivity. (2012)
  • Author(s): Ichikawa, K., Kagamu, H., Koyama, K., Miyabayashi, T., Koshio, J., Miura, S., Watanabe, S., Yoshizawa, H. and Narita, I.
  • Journal Title: Vaccine Volume: 30 Issue: 43 Pages: 6190-7
  • DOI: 10.1016/j.vaccine.2012.07.060
  • Peer Reviewed
• [Journal Article] Quality of Life with Gefitinib in Patients with EGFR-Mutated Non-Small Cell Lung Cancer : Quality of Life Analysis of North East Japan Study Group 002 Trial (2012)
  • Author(s): Oizumi S, Kobayashi K, Inoue A, Maemondo M, Sugawara S, Yoshizawa H, Isobe H, Harada M, Kinoshita I, Okinaga S, Kato T, Harada T, Gemma A, Saijo Y, Yokomizo Y, Morita S, Hagiwara K, Nukiwa T.
  • Journal Title: Oncologist Volume: 17 Issue: 6 Pages: 863-70
  • DOI: 10.1634/theoncologist.2011-0426
  • Peer Reviewed
• [Presentation] DEAD/H (Asp-Glu-Ala-Asp/His) box polypeptide 3, X-linked plays an oncogenic roles to induce cancer stem cell-like properties (2012)
  • Author(s): Nozaki K, Kagamu H,Yoshizawa H. et al.
  • Organizer: 2012 ESMO Congress
  • Place of Presentation: ウイーン、オーストリア
• [Presentation] Gefitinib for non-small cell lung cancer (NSCLC) with minor EGFR mutations: A retrospective study from the North East Japan Study Group (NEJ) (2012)
  • Author(s): Watanabe S, Yoshizawa H. et al.
  • Organizer: 2012 ESMO Congress
  • Place of Presentation: ウイーン、オーストリア
• [Presentation] The efficacy of triplet antiemetic therapy for chemotherapy-induced nausea and vomiting in lung cancer patients receiving highly emetogenic chemotherapy: palonosetron (PALO), aprepitant (APR), and dexamethasone (DEX) (2012)
  • Author(s): Yoshizawa H. et al.
  • Organizer: 2012 ESMO Congress
  • Place of Presentation: ウイーン、オーストリア
• [Presentation] Rondomized phase II study of concurrent gefitinib plus chemotherapy versus alteration of gefitinib and chemotherapy in previously untreated non small cell lung cancer with sensitive EGFR-mutations:NEJ 005/TCOG 0902 (2012)
  • Author(s): Oizumi S ,Yoshizawa H. et al.
  • Organizer: 第10回臨床腫瘍学会学術総会
  • Place of Presentation: 大阪