Investigation of mechanism mediating resistant phenotype of renal cell carcinoma to tyrosine kinase inhibitors and development of novel therapy to ovetrcome its resistance

• Project/Area Number: 24592389
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Urology
• Research Institution: Kobe University
• Principal Investigator: MIYAKE Hideaki 神戸大学, 医学(系)研究科(研究院), 准教授 (60379435)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2013: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000); Fiscal Year 2012: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 腎細胞癌 / チロシンキナーゼ阻害剤 / MAP kinase / Akt / 耐性獲得

Outline of Final Research Achievements

We demonstrated that the acqusition of phenotype in renal cell carcinoma cells resistant to tyrosine kinase inhibitors could be achieved by the maintained activation of MAP kinase and Akt, and that the additional treatment of renal cell carcinoma cells with specific inhibitors for MAP kinase or Akt was shown to contribute to overcome the resistance to tyrosine kinase inhibitors.
In addition, the measurement of serum MMP-9/TIMP-2 ratio in patients with renal cell carcinoma treated with sunitinib appeared to be useful for the early diagnosis with the acquired resistance to sunitinib in these patients.

Research Products

• [Journal Article] Characterization of mechanism involved in acquired resistance to sorafenib in a mouse renal cell cancer RenCa model (2014)
  • Author(s): Harada K, Miyake H, Kusuda Y, Fujisawa M
  • Journal Title: Clinical and Translational Oncology Volume: 16 Issue: 9 Pages: 801-806
  • DOI: 10.1007/s12094-013-1151-9
  • Peer Reviewed
• [Journal Article] Significance of circulating matrix metalloproteinase-9 to tissue inhibitor of metalloproteinases-2 ratio as a predictor of disease progression in patients with metastatic renal cell carcinoma receiving sunitinib (2014)
  • Author(s): Miyake H, Nishikawa M, Tei H, Furukawa J, Harada K, Fujisawa M
  • Journal Title: Urologic Oncology Volume: 32 Issue: 5 Pages: 584-588
  • DOI: 10.1016/j.urolonc.2014.01.016
  • Peer Reviewed
• [Journal Article] Expression of molecular markers associated with the mammalian target of rapamycin pathway in nonmetastatic renal cell carcinoma: Effect on prognostic outcomes following radical nephrectomy. (2014)
  • Author(s): Nishikawa M, Miyake H, Harada K, Fujisawa M
  • Journal Title: Ｕｒｏｌ Ｏｎｃｏｌ Volume: 32 Issue: 1 Pages: 49.e15-49.e21
  • DOI: 10.1016/j.urolonc.2013.07.014
  • Peer Reviewed
• [Journal Article] Acquired resistance to sunitinib in human renal cell carcinoma cells is mediated by constitutive activation of signal transduction pathways associated with tumour cell proliferation. (2013)
  • Author(s): Sakai I, Miyake H, Fujisawa M
  • Journal Title: Br J Urol Int Volume: ？ Issue: 2
  • DOI: 10.1111/j.1464-410x.2012.11655.x
  • Peer Reviewed