Development of hormesis suppression therapy as a new class of anticancer drug for lung cancer

• Project/Area Number: 15K10268
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Wakayama Medical University
• Principal Investigator: Ohashi Takuya 和歌山県立医科大学, 医学部, 助教 (90644518)
• Co-Investigator(Kenkyū-buntansha): 村垣 泰光 和歌山県立医科大学, 医学部, 教授 (40190904) ; 吉増 達也 和歌山県立医科大学, 医学部, 准教授 (60316099) ; 佐藤 冬樹 和歌山県立医科大学, 医学部, 講師 (60400131)
• Project Period (FY): 2015-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥5,070,000 (Direct Cost: ¥3,900,000、Indirect Cost: ¥1,170,000); Fiscal Year 2018: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2017: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: hormesis / dose-response curve / HDRA / 抗癌剤 / 肺癌 / 乳癌 / ホルミシス現象

Outline of Final Research Achievements

In the treatment of cancer, little is known about hormesis, growth stimulation at low doses and inhibition at higher doses, on cancer cell proliferation. We evaluated the hormetic dose-response relationships of anticancer agents for lung cancer. A549 lung cancer cell line showed a hormesis to anticancer agents in vitro. In addition, we evaluated hormetic dose-response relationship of anticancer agents using surgically resected specimens from non-small-cell lung cancer (NSCLC) or breast cancer patients on the basis of histoculture drug response assay (HDRA). Hormesis was observed in some cases. These specimens were thus resistant to the anticancer drugs because of the hormesis. HDRA is reliable to evaluate chemosensitivity, so we believe that hormesis occur in patients with malignant tumors. Tumor growth may be stimulated in patients who are resistant to anticancer agents.

Academic Significance and Societal Importance of the Research Achievements

抗癌剤治療は最大耐容量での投与が推奨されている。しかし高齢者の多い肺癌患者においては止むなく減量が行われることが多い。増殖抑制効果のある治療では低用量で投与した場合、逆に増殖促進効果を示すことがあり、hormesisと呼ばれている。減量投与の可能性の高い疾患においては無視できない事象であるにも関わらず、抗癌剤においてはこれまで検討されていない。本研究では、各種抗癌剤のhormesis現象を定量化するとともに、関与する因子を同定することで、それを特異的に抑制して抗癌剤治療効果を増強させる標的分子を定め、全く新しいがん治療のシーズを見出す。

Research Products

• [Journal Article] A theoretical model for the hormetic dose-response curve for anticancer agents. (2015)
  • Author(s): Yoshimasu T, Ohashi T, Oura S, Kokawa Y, Kawago M, Hirai Y, Miyasaka M, Nishiguchi H, Kawashima S, Yata Y, Honda M, Fujimoto T, Okamura Y.
  • Journal Title: Anticancer Research Volume: 35 Pages: 5851-585
  • Peer Reviewed
• [Presentation] Hormetic dose-response curve of cisplatin measured by histoculture drug response assay. (2017)
  • Author(s): Yoshimasu T, Oura S, Kawago M, Hirai Y, Miyasaka M, Ohashi T, Nishiguchi H, Yata Y, Honda M, Aoishi Y, Oku A, Fusamoto A, Nishimura Y
  • Organizer: 24th Asia Pacific Cancer Conference
  • Int'l Joint Research
• [Presentation] Bystander effect in antiestrogen therapy for breast cancer (2017)
  • Author(s): Aoishi Y, Yoshimasu T, Oura S, Kawago M, Hirai Y, Miyasaka M, Nishimura Y
  • Organizer: 24th Asia Pacific Cancer Conference
  • Int'l Joint Research
• [Presentation] 乳癌抗エストロゲン療法における bystander effect の検証 (2017)
  • Author(s): 青石裕香, 吉増達也, 尾浦正二, 粉川庸三, 平井慶充, 宮坂美和子, 西口春香, 矢田由美, 本田麻里子, 奥あや, 西村好晴
  • Organizer: 第25回日本乳癌学会学術総会
• [Presentation] Quantitative evaluation for hormetic reactions of anticancer agents for lung cancer. (2016)
  • Author(s): Yoshimasu T, Oura S, Kokawa Y, Kawago M, Miyasaka M, Ohashi T, Yata Y, Okamura Y.
  • Organizer: The 24th Annual Meeting of Asian Society for Cardiovascular and Thoracic Surgery
  • Place of Presentation: Taipei, Taiwan
  • Year and Date: 2016-04-06
  • Int'l Joint Research