Development of iron control cancer therapy

• Project/Area Number: 26861048
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Okayama University
• Principal Investigator: TOSHIAKI OHARA 岡山大学, 医歯(薬)学総合研究科, 助教 (40623533)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2014: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 鉄 / 除鉄 / 肝臓癌 / ソラフェニブ / 鉄キレート / デフェラシロックス / 癌 / 血管新生阻害薬 / 血管新生 / 分子標的薬

Outline of Final Research Achievements

Iron overload is known to cause cancer. We previously reported that iron depletion inhibited cancer cell proliferation and conversely induced angiogenesis. Since sorafenib has an anti-angiogenic effect by its inhibitory targeting VEGFR, we hypothesized that sorafenib could complement the anti-cancer effect of iron depletion. Human hepatocarcinoma HepG2 and HLE cells were used in this study. Deferasirox, iron chelator, enhanced the inhibitory effect of sorafenib on cell viability. Sorafenib combined with deferasirox synergistically inhibited the cell cycle and induced apoptosis. We retrospectively investigated HCC patients that were treated with sorafenib (n=58). Low iron conditions (high TIBC and low ferritin groups) prolonged overall survival. These results suggested that ron depletion by deferasirox has the potential to be a novel combination chemotherapy with sorafenib in clinical study.

Research Products

• [Journal Article] Iron depletion enhances the effect of sorafenib in hepatocarcinoma (2016)
  • Author(s): Shinichi Urano, Toshiaki Ohara, Kazuhiro Noma, Ryoichi Katsube, Takayuki, Ninomiya, Yasuko Tomono, Hiroshi Tazawa, Shunsuke Kagawa, Yasuhiro Shirakawa, Fumiaki, Kimura, Kazuhiro Nouso, Akihiro Matsukawa, Kazuhide Yamamoto & Toshiyoshi Fujiwara
  • Journal Title: Cancer Biology & Therapy Volume: Epub ahead Issue: 6 Pages: 648-656
  • DOI: 10.1080/15384047.2016.1177677
  • Peer Reviewed / Acknowledgement Compliant
• [Presentation] 肝細胞癌に対する除鉄剤の臨床投与経験 (2015)
  • Author(s): 大原利章、二宮卓之、友野靖子、木村文昭
  • Organizer: 第39回日本鉄バイオサイエンス学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2015-08-29
• [Presentation] 固形癌に対する除鉄誘導による血管新生阻害薬併用療法の確立 (2014)
  • Author(s): 大原利章、木村文昭、浦野真一、二宮卓之、勝部亮一、野間和広、友野靖子、藤原俊義、松川昭博
  • Organizer: 第38回日本鉄バイオサイエンス学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2014-09-06 – 2014-09-07
• [Presentation] Iron chelation therapy increased the anticancer effect of sorafenib in hepatocarcinoma (2014)
  • Author(s): Shinichi Urano, Toshiaki Ohara, Ryoichi Katsube, Kazuhiro Noma, Yasuko Tomono, Hiroshi Tazawa, Kazuhiro Nouso, Yasuhiro Shirakawa, Toshiyoshi Fujiwara
  • Organizer: 105th Annual Meeting American Association for Cancer Research
  • Place of Presentation: サンディエゴ(米国)
  • Year and Date: 2014-04-05 – 2014-04-09