Mechanism of lenvatinib resistance in HCC-CSCs

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K17039
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53010:Gastroenterology-related
• Research Institution: Hokkaido University
• Principal Investigator: Maehara Osamu 北海道大学, 薬学研究院, 助教 (80836338)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 癌幹細胞

Outline of Final Research Achievements

The following is a list of results achieved throughout the study period.
(1) Lenvatinib and sorafenib resistant cells were generated against HCC cell lines. (2)The ratio of CSCs (CD133high/CD44high) in resistant cells was different between sor- and len-resistant cells, suggesting that the nature of resistance differs between the two cell lines.(3) Although sor- and len-resistant cells had superior tumorigenic potential compared to their parent cells, there was no significant difference between the resistant cells.(4)The results of in vitro analysis of the effects of candidate genes common to resistant cells on resistance suggested that candidate genes A, B, and C may be involved in resistance in a concerted manner.

Free Research Field

腫瘍生物学

Academic Significance and Societal Importance of the Research Achievements

HCCにおいてsorafenib耐性細胞とCSCsとの関連を報告した研究は数多く存在する一方で、lenvatinib耐性細胞の性質やCSCsとの関係性を検証した報告はこれまでに報告が少なかった。さらに、それぞれの薬剤の耐性細胞同士を比較検討した報告もなかったため本研究を実施した。実際、lenvatinib耐性細胞とsorafenib耐性細胞の性質やCSCsとの関係性には特異性と共通性があることが一部ではあるが明らかになった。この解明は、lenvatinib不応例を含むHCCに対する治療最適化や新規治療法開発に繋がることが期待される。