Development of adaptive therapy targeting MUC-1C in colorectal cancer with acquired anti-EGFR antibody resistance

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07675
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Osaka International Cancer Institute
• Principal Investigator: Matsuda Chu 地方独立行政法人大阪府立病院機構大阪国際がんセンター(研究所), その他部局等, 消化器外科副部長 (00379207)
• Co-Investigator(Kenkyū-buntansha): 植村 守 大阪大学, 大学院医学系研究科, 講師 (10528483) ; 平木 将之 大阪大学, 大学院医学系研究科, 招へい教員 (80621036)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 大腸癌 / MUC1 / 治療抵抗性 / 腫瘍内不均一性

Outline of Final Research Achievements

Our study was designed to examine the association of MUC1 with intratumoral heterogeneity and drug-resistant clones in metastatic colorectal cancer with acquired anti-EGFR antibody resistance.
Long-term exposure of colon cancer cell lines to L-OHP and 5FU, which are cytotoxic anticancer drugs, established drug-resistant strains. We confirmed that the anti-EGFR antibody-resistant colon cancer cell line LIM1215 has resistance to the anti-EGFR antibody. In order to investigate changes in MUC1 until the acquisition of resistance, we analyzed the MUC1 in short-term exposure strains, and confirmed increased expression of MUC1. Other downstream molecules are currently under investigation. Single-cell analysis was performed to investigate the association of MUC1 with intratumoral heterogeneity and mutational status of EGFR signaling. We are currently analyzing the data.

Free Research Field

大腸癌　低侵襲手術　化学療法

Academic Significance and Societal Importance of the Research Achievements

大腸癌薬剤耐性株を作成し、短期暴露株においてMUC1発現増加を確認した。長期暴露株については現在解析中である。腫瘍内不均一性を詳細な解析し、原発巣と肝転移巣の発現型の違いを明らかにし、MUC1との関連性を明らかにする。MUC1による薬剤耐性クローンの制御が可能か検証し、MUC1を標的とした個別化医療Precision Medicineの確立へつながる可能性を模索していく。