Exploring novel therapeutic strategies targeting the RAS for advanced bladder cancer

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16805
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Kagoshima University
• Principal Investigator: MATSUSHITA Ryosuke 鹿児島大学, 医歯学域医学系, 助教 (80735366)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 膀胱癌

Outline of Final Research Achievements

As a result of this study, we previously performed IC50 measurements and RNAseq analysis on gemcitabine- and cisplatin-resistant cells using two bladder cancer cell lines (BOY and T24) in our laboratory, but gemcitabine- and cisplatin-resistant bladder cancer However, no cross-resistance was observed in gemcitabine- and cisplatin-resistant bladder cancer cells. Therefore, we performed functional analysis using novel RAS inhibitors, which showed antitumor effects against these resistant cell lines. Furthermore, RNAseq analysis using pan-RAS inhibitor-treated cells confirmed that many genes were dramatically repressed, especially pathways involved in the cell cycle and cell division, which were regulated by the inhibitor.

Free Research Field

泌尿器癌

Academic Significance and Societal Importance of the Research Achievements

進行性膀胱癌の予後は不良であるが、その理由としてファーストラインとして使用されている抗癌剤治療であるGC療法（Gemcitabine + Cisplatin）の効果が限定的であることが、挙げられる。そして、膀胱癌は他の泌尿器癌（前立腺癌や腎癌）に比べて明らかに治療手段が少なく、治療耐性獲得機序の解明や新規治療戦略の開拓が極めて重要と考えられる。本研究で我々は、薬剤感受性並びに耐性膀胱癌における新規RAS阻害剤によるRASを標的とした治療の可能性の探索と、それらに関わる癌シグナル経路を提示した。その為、新たな治療戦略の基礎データを提示することができたと考える。