Development of ferroptosis induction therapy against KRAS altered gastric cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16413
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyoto University
• Principal Investigator: Kikuchi Osamu 京都大学, 医学研究科, 助教 (10869366)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 分子標的療法 / KRAS

Outline of Final Research Achievements

We performed a genome-wide CRISPR screening and confirmatory experiments on KRAS-amplified cells, identifying multiple candidate gene knockouts that may enhance anti-tumor effects of MEK inhibitors and those that may attenuate anti-tumor effects. Among these, inhibition of GPX4 showed good anti-tumor effects in combination with MEK inhibitors. In the future, we will plan to run additional pre-clinical studies in mice and human clinical studies (phase I / II) to continue development for new treatment regimens.

Free Research Field

消化器癌

Academic Significance and Societal Importance of the Research Achievements

切除不能進行胃癌の治療成績は不十分であるが、こうした難治性の胃癌の治療法開発に貢献する研究結果を得た。また今回開発している治療戦略は、胃癌の既存の標準治療で用いる薬剤とは異なるため、既存の標準治療法を使い切った胃癌症例へのさらなる生存期間延長にも貢献する可能性がある。