Establishment of the biomarker with nanoparticles for the diagnosis and the treatment of pancreatic cancer

• Project/Area Number: 24591018
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Tokyo Medical University
• Principal Investigator: ITOI Takao 東京医科大学, 医学部, 准教授 (60338796)
• Co-Investigator(Kenkyū-buntansha): MIYAZAWA Keisuke 東京医科大学, 医学部, 教授 (50209897) ; YOKOYAMA Tomohisa 東京医科大学, 医学部, 兼任講師 (40408240)
• 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: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2012: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: オートファジー / 上皮成長因子受容体 / マクロライド化合物 / 小胞体ストレス / アポトーシス / ネクロプトーシス / 膵臓癌 / チロシンキナーゼ阻害剤 / マクロライド / ERストレス / 膵癌 / ナノ粒子 / Drug Delivery System

Outline of Final Research Achievements

EGFR-TKI induced autophagy with a pro-survival role. The macrolides inhibiting the autophagy flex exhibited the enhanced cytotoxicity in pancreatic cancer cell lines. Therefore, it suggests the possibility of using macrolide as an autophagy inhibitor and a “chemosensitizer” for EGFR-TKI-therapy in pancreatic cancer patients. This pronounced cytotoxicity was not due to up-regulation of apoptosis induction but appeared to be medicated through necroptosis at least in part. It will be important to establish the underlying molecular mechanism of the enhanced non-apoptotic cell death as well as identification of the targets of macrolides.