Liver cancer drug resistance through Nrf2 dependence in tumor microenvironment

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16381
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55010:General surgery and pediatric surgery-related
• Research Institution: The University of Tokushima
• Principal Investigator: TERAOKU Hiroki 徳島大学, 病院, 特任助教 (80737106)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: Nrf2 / 薬剤耐性 / 肝細胞癌 / 腫瘍微小環境 / CAF

Outline of Final Research Achievements

Acquisition of drug resistance in cancer is an important issue in drug therapy for hepatocellular carcinoma, for which novel immunotherapy are rapidly progressing in recent years. In this study, we focused on the mechanism of malignancy acquisition in the tumor microenvironment, including hepatocellular carcinoma cells and cancer-associated fibroblasts (CAFs). We succeeded in creating sorafenib/lenvatinib-resistant liver cancer cells respectively, and found that the interaction between cancer cells and CAFs plays an important role through Nuclear Factor(erythroid-derived 2)-Like 2 (Nrf2) in the acquisition of drug resistance.

Free Research Field

肝細胞癌、腫瘍微小環境、薬剤耐性

Academic Significance and Societal Importance of the Research Achievements

癌細胞自身に対する薬剤耐性メカニズムは研究が進んでいるが、癌細胞の悪性度獲得において重要な役割を果たす腫瘍微小環境が薬剤耐性に与える影響については不明な点が多い。近年急速に新たな治療が進んでいる肝細胞癌に対する薬物療法において、腫瘍微環境構築の根幹となるCancer cell-CAF interactionを解除し、薬剤耐性に対する治療戦略確立を目指すことの社会的意義は大きく、癌人口が増加の一途をたどるの現状を考慮すると、本研究は腫瘍微小環境の糸口となる治療法開発につながる可能性があり意義は大きいと考える。