Analysis of metabolic changes associated with cetuximab resistance in oral squamous cell carcinoma and designing of new treatment

• Project/Area Number: 16K20613
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Surgical dentistry
• Research Institution: Keio University
• Principal Investigator: Yoshikawa Momoko 慶應義塾大学, 医学部(信濃町), 訪問研究員 (50570967)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000); Fiscal Year 2017: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2016: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: CD44v / 口腔扁平上皮癌 / セツキシマブ / セツキシマブ耐性 / CD44ｖ

Outline of Final Research Achievements

Our group established cetuximab-resistant cells by using oral squamous cell carcinoma cells expressing CD44v, which is cancer stem cell marker. We also found that cetuximab-resistant cells had high activity of metabolic pathways different from those of the original cell strain by metabolic analysis. We continue to analyze at the molecular level of the metabolic changes associated with cetuximab resistance, and aim at developing new treatments for cetuximab refractory cases.

Academic Significance and Societal Importance of the Research Achievements

セツキシマブ耐性化に伴う分子機構の解析を行うことで、セツキシマブ不応症例に対する新規治療法の開発および患者個別の治療法の可能性も示唆された。

Research Products

• [Journal Article] Recurrent Spindle Cell Carcinoma Shows Features of Mesenchymal Stem Cells (2018)
  • Author(s): Ouchi T.、Morikawa S.、Shibata S.、Takahashi M.、Yoshikawa M.、Soma T.、Miyashita H.、Muraoka W.、Kameyama K.、Kawana H.、Arima Y.、Saya H.、Okano H.、Nakagawa T.、Asoda S.
  • Journal Title: J Dent Res Volume: ー Issue: 7 Pages: 779-786
  • DOI: 10.1177/0022034518759278
  • Peer Reviewed / Open Access
• [Journal Article] Eradication of CD44-variant positive population in head and neck tumors through controlled intracellular navigation of cisplatin-loaded nanomedicines (2016)
  • Author(s): Ming Wang, Yutaka Miura, Kenji Tsuchihashi, Kazuki Miyano, Osamu Nagano, Momoko Yoshikawa, Ami Tanabe, Jun Makino, Yuki Mochida, Nobuhiro Nishiyama, Hideyuki Saya, Horacio Cabral, Kazunori Kataoka
  • Journal Title: Journal of Controlled Release Volume: 230 Pages: 26-33
  • DOI: 10.1016/j.jconrel.2016.03.038
  • Peer Reviewed / Int'l Joint Research