To provide a biomarker for predicting the therapeutic effect of chemotherapy to lung cancer harboring EGFR mutation.

• Project/Area Number: 24701037
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Clinical oncology
• Research Institution: Kinki University
• Principal Investigator: KANEDA Hiroyasu 近畿大学, 医学部, 講師 (50351599)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: 化学療法 / 抗がん剤耐性 / EMT / ＥＭＴ

Outline of Final Research Achievements

Non-small-cell lung cancer (NSCLC) has a poor prognosis and remains the leading cause of death related to cancer. The discovery of both activating mutations in the EGFR gene in 2004 and EML4-ALK in 2007 have been found. EGFR tyrosine kinase inhibitor (TKI) and ALK TKI results in dramatically high response rates and prolonged progression-free survival compared with standard chemotherapy in NSCLC patients harboring gene alteration.
However, almost patients eventually develop acquired resistance to these drugs within 1 year. In addition, 20%-30% of NSCLC patients with EGFR mutations do not show an initial response to EGFR-TKIs. Several mechanisms of acquired resistance to EGFR-TKIs were found but not all. We found that forkhead box Q1 (FOXQ1) is overexpressed in lung cancer and enhances tumorigenicity and tumor growth presumably through its angiogenic and antiapoptotic effects in this research. Furthermore, FOXQ1 has a role of regulating drug resistance and aggressiveness in lung cancer.

Research Products

• [Journal Article] Risk factors for cisplatin-induced nephrotoxicity and potential of magnesium supplementation for renal protection. (2014)
  • Author(s): Kidera Y, Kawakami H, Sakiyama T, Okamoto K, Tanaka K, Takeda M, Kaneda H, Nishina S, Tsurutani J, Fujiwara K, Nomura M, Yamazoe Y, Chiba Y, Nishida S, Tamura T, Nakagawa K.
  • Journal Title: PLoS One Volume: 9(7) Issue: 7 Pages: e101902-e101902
  • DOI: 10.1371/journal.pone.0101902
  • Peer Reviewed / Open Access
• [Journal Article] Multiplex genomic profiling of non-small cell lung cancers from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin: results of a West Japan Oncology Group study. (2014)
  • Author(s): Okamoto I, Sakai K, Morita S, Yoshioka H, Kaneda H, Takeda K, Hirashima T, Kogure Y, Kimura T, Takahashi T, Atagi S, Seto T, Sawa T, Yamamoto M, Satouchi M, Okuno M, Nagase S, Takayama K, Tomii K, Maeda T, Oizumi S, Fujii S, Akashi Y, Nishino K, Ebi N, Nakagawa K, Nakanishi Y, Nishio K.
  • Journal Title: Oncotarget Volume: 5(8) Pages: 2293-2304
  • Peer Reviewed / Open Access
• [Journal Article] A phase 1 study of linifanib in combination with carboplatin/paclitaxel as first-line treatment of Japanese patients with advanced or metastatic non-small cell lung cancer (NSCLC). (2014)
  • Author(s): Horinouchi H, Yamamoto N, Nokihara H, Horai T, Nishio M, Ohyanagi F, Horiike A, Nakagawa K, Terashima M, Okabe T, Kaneda H, McKee MD, Carlson DM, Xiong H, Tamura T.
  • Journal Title: Cancer Chemother Pharmacol Volume: 74(1) Issue: 1 Pages: 37-43
  • DOI: 10.1007/s00280-014-2478-9
  • Peer Reviewed / Open Access
• [Journal Article] Activation of HER family signaling as a mechanism of acquired resistance to ALK inhibitors in EML4-ALK-positive non-small cell lung cancer. (2012)
  • Author(s): Tanizaki J, Okamoto I, Okabe T, Sakai K, Tanaka K, Hayashi H, Kaneda H, Takezawa K, Kuwata K, Yamaguchi H, Hatashita E, Nishio K, Nakagawa K.
  • Journal Title: Clin Cancer Res Volume: 18(22) Pages: 6219-6226
  • Peer Reviewed
• [Journal Article] A novel mass spectrometry-based assay for diagnosis of EML4-ALK-positive non-small cell lung cancer. (2012)
  • Author(s): Sakai K, Okamoto I, Takezawa K, Hirashima T, Kaneda H, Takeda M, Matsumoto K, Kimura H, Fujita Y, Nakagawa K, Arao T, Nishio K.
  • Journal Title: J Thorac Oncol Volume: 7(5) Pages: 913-918
  • Peer Reviewed
• [Journal Article] Pilot study of duloxetine for cancer patients with neuropathic pain non-responsive to pregabalin. (2012)
  • Author(s): Matsuoka H, Makimura C, Koyama A, Otsuka M, Okamoto W, Fujisaka Y, Kaneda H, Tsurutani J, Nakagawa K.
  • Journal Title: Anticancer Res Volume: 32(5) Pages: 1805-1809
  • Peer Reviewed
• [Journal Article] Pharmacokinetics of docetaxel in a patient with non-small cell lung cancer undergoing continuous ambulatory peritoneal dialysis. (2012)
  • Author(s): Kaneda H, Okamoto I, Nakagawa K.
  • Journal Title: J Thorac Oncol Volume: 7(3) Pages: 621-622
  • Peer Reviewed
• [Journal Article] Marked response to both S-1 and pemetrexed in a patient with echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-positive lung adenocarcinoma. (2012)
  • Author(s): Kaneda H, Okamoto I, Sakai K, Tanizaki J, Takeda M, Nishio K, Nakagawa K.
  • Journal Title: Acta Oncol Volume: 51(7) Pages: 942-944
  • Peer Reviewed
• [Journal Article] SRPX2 is a novel chondroitin sulfate proteoglycan that is overexpressed in gastrointestinal cancer. (2012)
  • Author(s): Tanaka K, Arao T, Tamura D, Aomatsu K, Furuta K, Matsumoto K, Kaneda H, Kudo K, Fujita Y, Kimura H, Yanagihara K, Yamada Y, Okamoto I, Nakagawa K, Nishio K.
  • Journal Title: PLoS One Volume: 7(1)
  • Peer Reviewed
• [Journal Article] Integrated analysis of whole genome exon array and array-comparative genomic hybridization in gastric and colorectal cancer cells. (2012)
  • Author(s): Furuta K, Arao T, Sakai K, Kimura H, Nagai T, Tamura D, Aomatsu K, Kudo K, Kaneda H, Fujita Y, Matsumoto K, Yamada Y, Yanagihara K, Sekijima M, Nishio K.
  • Journal Title: Cancer Sci Volume: 103(2) Pages: 221-227
  • Peer Reviewed
• [Journal Article] Aza-derivatives of resveratrol are potent macrophage migration inhibitory factor inhibitors. (2012)
  • Author(s): Fujita Y, Islam R, Sakai K, Kaneda H, Kudo K, Tamura D, Aomatsu K, Nagai T, Kimura H, Matsumoto K, de Velasco MA, Arao T, Okawara T, Nishio K.
  • Journal Title: Invest New Drugs Volume: 30(5) Pages: 1878-1886
  • Peer Reviewed
• [Journal Article] Reversible posterior leukoencephalopathy syndrome and trastuzumab. (2012)
  • Author(s): Kaneda H, Okamoto I, Satoh T, Nakagawa K.
  • Journal Title: Invest New Drugs Volume: 30(4) Pages: 1766-1767
  • Peer Reviewed
• [Presentation] Phase II study of erlotinib plus tivantinib in patients with EGFR mutation-positive NSCLC who failed in immediately previous EGFR-TKI therapy. (2014)
  • Author(s): Kaneda H
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] Phase I study of CO-1686 (rociletinib), an irreversible, mutant-selective inhibitor of EGFR mutations, in Japanese patients with T790M-positive NSCLC. (2014)
  • Author(s): Kaneda H
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] Update of Nintedanib (BIBF1120). (2014)
  • Author(s): Kaneda H
  • Organizer: 第55回日本肺癌学会学術集会
  • Place of Presentation: 国立京都国際会館
  • Year and Date: 2014-11-14 – 2014-11-16
• [Presentation] Clinical benefit of continued therapy with crizotinib beyond initial disease progression in advanced ALK-positive NSCLC. (2014)
  • Author(s): Kaneda H
  • Organizer: 第12回日本臨床腫瘍学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] Tumor genomic profiling of non-small cell lung cancers (NSCLC) from the LETS phase III trial of first-line S-1/carboplatin versus paclitaxel/carboplatin. (2014)
  • Author(s): Kaneda H
  • Organizer: 第12回日本臨床腫瘍学会
  • Place of Presentation: 福岡国際会議場
  • Year and Date: 2014-07-17 – 2014-07-19
• [Presentation] Phase I study of Patritumab (U3-1287) in combination with Erlotinib in NSCLC patients. (2013)
  • Author(s): 金田裕靖・中川和彦・工藤慶太・西尾誠人・村上晴泰・山本信之・堀之内秀仁・田村友秀
  • Organizer: 第54回日本肺癌学会総会
  • Place of Presentation: ホテルニューオータニ（東京都千代田区）
• [Presentation] Phase I study of ombrabulin , a vascular disrupting agent (VDA) in Japanese patients with advanced solid tumors. (2012)
  • Author(s): Murakami H, Kurata T, Fujisaka Y, Hayashi H, Tanaka K, Kaneda H, Nakagawa K, Yokota T, Boku N, Yamamoto N.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] Antitumor action of the MET tyrosine kinase inhibitor crizotinib in gastric cancer positive for MET amplification. (2012)
  • Author(s): Okamoto W, Okamoto I, Arao T, Sakai K, Okamoto K, Kawakami H, Kaneda H, Nishina S, Tsurutani J, Kurata T, Yanagihara K, Nishio K, and Nakagawa K.
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌市
• [Presentation] A phase III study comparing amrubicin and cisplatin (AP) with irinotecan and cisplatin (IP) for the treatment of extended-stage small cell lung cancer (ED-SCLC): JCOG0509. (2012)
  • Author(s): Kaneda H, Kotani Y, Satouchi M, Ando M, Yamamoto N, Ichinose Y, Ohe Y, Nishio M, Hida T, Takeda K, Kudoh S, Minato K, Shibata T, and Tamura T.
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪市
• [Presentation] Overexpression of FOXQ1 is important factor in tumorigenecity and tumor growth. (2012)
  • Author(s): Kaneda H, Arao T, Tanaka K, Matsumoto K, Kimura H, Nagai T, Sakai K, Fujita Y, de Velasco MA, Yamada Y, Tsurutani J, Okamoto I, Nakagawa K, and Nishio K.
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪市
• [Presentation] Activin-A directly inhibits vascular endothelial cell growth via TGF-β dependent signal pathway. (2012)
  • Author(s): Kaneda H, Arao T, Tanaka K, Matsumoto K, Kimura H, Nagai T, Fujita Y, de Velasco MA, Yamada Y, Okamoto I, Nakagawa K, and Nishio K.
  • Organizer: 第10回日本臨床腫瘍学会学術集会
  • Place of Presentation: 大阪市
• [Presentation] Chemotherapy with CPT-11 after gemcitabine failure in patients with advanced pancreatic cancer.
  • Author(s): Kaneda H, Ueda S, Kawakami H, Tanizaki J, OkamotoK, Makimura C, Tanaka K, Matsuoka M, Okamoto W, Shimizu T, Fujisaka Y, Nishina S, Miyazaki M, Tsurutani J, Kurata T, Okamoto I, Nakagawa K.
  • Organizer: 14th World Congress of Gastorientestinal Cancer
  • Place of Presentation: スペイン バルセロナ
• [Presentation] Second-line chemotherapy with S-1 after cisplatin and gemcitabine failure in patients with advance biliary tract cancer.
  • Author(s): Ueda S, Kawakami H, Okamoto W, Nishina S, Kudo T, Makimura C, Kiyota H, Tanaka K, Kaneda H, Fujisaka Y, Miyazaki M, Tsurutani J, Okamoto I, Kurata T, and Nakagawa K.
  • Organizer: 14th World Congress of Gastorientestinal Cancer
  • Place of Presentation: スペイン バルセロナ