Diagnostic and therapeutic approaches targeting chromosomal instability

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09109
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Jichi Medical University
• Principal Investigator: SUZUKI KOICHI 自治医科大学, 医学部, 教授 (70332369)
• Co-Investigator(Kenkyū-buntansha): 力山 敏樹 自治医科大学, 医学部, 教授 (80343060)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 染色体不安定性 / セントロメア / Satellite α tanscript / 薬剤感受性 / 大腸癌

Outline of Final Research Achievements

We demonstrated that chromosomal instability (CIN) induced by an administration of DNA demethylating agent made pancreatic cancer cells to be more invasive phenotype. Occult metastasis is often identified during surgery in pancreatic cancer patients whose tumor specimens show high degree of demethylation, and these patients show poor prognosis.
In addition, we verified that CIN was involved in drug sensitivity. We constructed retroviral vectors expressing major satellite, infected a microsatellite stable mouse colon cancer cell line to induce CIN.
Induction of CIN led to increased sensitivity to topoisomerase I inhibitors, indicating its potential to overcome drug resistance.

Free Research Field

分子腫瘍学

Academic Significance and Societal Importance of the Research Achievements

本研究では、SatAが誘導する染色体不安定性が癌の進展、特に転移形成にどのように関わるのか我々のこれまでの研究課題を発展させると共に、染色体不安定性の臨床的意義を異なる視点から見直す事で、診断や治療の新たなアプローチに展開しようとするものです。染色体不安定性という生物学的悪性度から評価する転移・再発の診断アプローチへの応用に加えて、免疫チェックポイント阻害剤の効果予測因子の確立、感受性亢進、耐性の克服といった新たな治療アプローチに展開できると期待されます。