The analysis of predictive markers for the efficacy of cisplatin and vinorelbine regimens as postoperative adjuvant chemotherapy of lung cancer

• Project/Area Number: 25462174
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kyoto University
• Principal Investigator: SONOBE Makoto 京都大学, 医学(系)研究科(研究院), 准教授 (00432378)
• Co-Investigator(Kenkyū-buntansha): DATE Hiroshi 京都大学, 大学院医学研究科, 教授 (60252962)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,510,000 (Direct Cost: ¥2,700,000、Indirect Cost: ¥810,000); Fiscal Year 2015: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 分子マーカー / 補助化学療法 / Saracatinib / VRB耐性株 / 非小細胞肺癌 / ビノレルビン / 薬剤耐性 / ABCB1

Outline of Final Research Achievements

Vinorelbine(VNR)-resistant lung cancer cell line has been made by step-by-step dose escalation method. Whole transcriptome was compared between the parental and the VNR-resistant lines using cDNA microarray. The comparison showed the significant increase of expression of ABCB1 transporter gene and extracellular matrix-integrin-Src pathway genes. The activation of ABCB1, multi-drug resistant, transporter was confirmed to be one of the main acquired resistant mechanisms. Furthermore, the association of focal adhesion pathways with VNR-resistant mechanism was analyzed. Both mechanisms synergistically affected on VNR resistance of lung cancer cells, and their concomittant inhibiton overcame the resistance. Clinical significance of the molecular expression of both pathways did not seen in the adjuvant settings of resected lung cancer patients. Our results were presented in some international or domestic conferences, and then, now prepared for being published.

Research Products

• [Journal Article] Video-assisted thoracoscopic lobectomy versus stereotactic radiotherapy for stage I lung cancer. (2015)
  • Author(s): Hamaji M, Chen F, Matsuo Y, Kawaguchi A, Morita S, Ueki N, Sonobe M, Nagata Y, Hiraoka M, Date H.
  • Journal Title: Ann Thorac Surg Volume: 99(4) Pages: 1122-9
  • Peer Reviewed
• [Journal Article] Association between epithelial-mesenchymal transition and cancer stemness and their effect on the prognosis of lung adenocarcinoma. (2015)
  • Author(s): 405.Sowa T, Menju T, Sonobe M, Nakanishi T, Shikuma K, Imamura N, Motoyama H, Hijiya K, Aoyama A, Chen F, Sato T, Kobayashi M, Yoshizawa A, Haga H, Sozu T, Date H.
  • Journal Title: Cancer Med Volume: 4(12) Pages: 1853-62
  • NAID: 120005971039
  • Peer Reviewed