Development of Predictive Markers for Sensitivity to Fibroblast Growth Factor Receptor Inhibitors Using Colorectal Cancer Stem Cells

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K20818
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0901:Oncology and related fields
• Research Institution: The Tazuke Kofukai
• Principal Investigator: Yamamoto Takehito 公益財団法人田附興風会, 医学研究所 腫瘍研究部, 研究員 (10909310)
• Project Period (FY): 2021-08-30 – 2023-03-31
• Keywords: 大腸癌 / 癌幹細胞 / スフェロイド / 線維芽細胞増殖因子受容体阻害薬 / FGFR阻害薬

Outline of Final Research Achievements

In this study, we searched for biomarkers that would identify colorectal cancer patients who respond to FGFR inhibitors. We cultured cancer cells in a 3D environment using resected tumors and established colorectal cancer stem cell spheroids in colorectal cancer patients who underwent tumor resection at our institution. Using these spheroids, we found that approximately 28% of RAS/RAF wild-type colorectal cancers were sensitive to FGFR inhibitors.
These results did not correlate with FGFR gene mutation, copy number, or expression level, indicating that it is difficult to predict sensitivity to FGFR inhibitors based on FGFR gene alterations alone. On the other hand, the ratio of the expression levels of the FGFR and EGFR genes, "F/E," was found to correlate significantly with the susceptibility levels of FGFR inhibitors, and this may be a biomarker for predicting FGFR inhibitor efficacy.

Free Research Field

大腸癌

Academic Significance and Societal Importance of the Research Achievements

線維芽細胞増殖因子受容体（FGFR）阻害薬は、新規分子標的治療薬として近年注目を集め、2019年以降、尿路上皮癌や胆道癌等に対して使用可能となってきた。しかし、大腸癌に対してFGFR阻害薬はまだ承認されておらず、その理由としてFGFR阻害薬が効果を示す大腸癌患者の抽出を可能とするバイオマーカーが未発見であることが挙げられる。
本研究では、FGFR遺伝子とEGFR遺伝子の発現レベル比「F/E」がFGFR阻害薬の感受性と相関する事実を見出し、「F/E」が新規バイオマーカーとなりうる可能性を示した。これは、FGFR阻害薬の大腸癌への臨床応用が可能となる重要な結果であると考える。