A novel cancer therapeutics with gene medicine and molecular targeted agents directing the p53 pathways in esophageal carcinoma

2016 Fiscal Year Final Research Report

• Project/Area Number: 26462000
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Digestive surgery
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Tagawa Masatoshi 千葉県がんセンター(研究所), がん治療開発グループ, 部長 (20171572)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 食道がん / p53経路 / 細胞障害活性 / アデノウイルス / 遺伝子医薬 / 分子標的薬

Outline of Final Research Achievements

Esophageal carcinoma remains intractable despite therapeutic multi-modality when it develops into an advanced case or became chemotherapy-resistant. A next-generation sequencing technique revealed that a majority of the patients in East Asia had aberration of p53 gene and the down-stream pathways, which consequently indicated that the p53 pathways was the major therapeutic target. We then investigated a novel therapeutic approach to augment the p53 pathways with gene medicine and a molecular targeted agent. Recombinant replicative adenoviruses (Ad) induced up-regulated p53 expression and produced cytotoxic effects on esophageal carcinoma cells. Transduction of the cells with the wild-type p53 gene increased the cytotoxicity but the replicative Ad numbers decreased. In contrast, molecular targeted agents which stabilize the wild-type p53 in the terms of ubiquitination or functionally convert mutated p53 into the wild-type were not effectively cytotoxic to esophageal carcinoma.

Free Research Field

遺伝子治療