Gene therapy development in liver cancer

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K08429
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Jikei University School of Medicine
• Principal Investigator: Oikawa Tsunekazu 東京慈恵会医科大学, 医学部, 講師 (20514491)
• Co-Investigator(Kenkyū-buntansha): 吉田 清嗣 東京慈恵会医科大学, 医学部, 教授 (70345312)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 肝癌 / がん幹細胞

Outline of Final Research Achievements

Liver cancers, including hepatocellular carcinoma (HCC) are among the most common cancers worldwide and are associated with a poor prognosis. The only curative treatments for HCC are surgical resection for early-stage. However, most patients are diagnosed at advanced-stages. For the treatment of unresectable HCC, transcatheter arterial chemoembolization and systemic chemotherapy, but the effects are limited. Therefore, the identification of novel molecules that can become targets for future therapies is urgently needed.
We have reported that dual-specificity tyrosine-regulated kinase 2 (DYRK2) functions as a tumor suppressor by regulating cell survival, differentiation, proliferation and apoptosis. We found that HCC patients with low levels of DYRK2 had a significantly worse overall survival than those with high levels. Overexpression of DYRK2 inhibited cell proliferation and induced apoptosis. The forced expression of DYRK2 may become a potential target for gene therapy of HCC.

Free Research Field

Gastroenterology

Academic Significance and Societal Importance of the Research Achievements

肝癌は全世界で第2位の死亡数をほこり、日本では男性は5位、女性は7位である。日本における肝癌の10年生存率は17.6％と膵癌に次ぐワースト第2位で予後不良である。肝癌の根治的治療としては切除が主体で、早期にはラジオ波焼灼療法、肝動脈塞栓療法、肝移植等が有効であるが、脈管浸潤や遠隔転移を有する症例の多くは予後不良であるため、より早期の診断法の確立と新規治療法が切望されている。本研究における我々の研究成果は学術誌(Yokoyama-Mashima S et al, Cancer Lett,2019)に採択され、肝癌における将来的な新規治療となりうる可能性を示しており有益な発見であると考える。