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<p>Despite advances in adjuvant therapy for colorectal cancer, tumor relapses, often driven by minimal residual disease, remain a formidable clinical challenge. The cancer stem cell hypothesis provides a key framework for understanding this problem, positing that a small, therapy-resistant subpopulation of cells drives recurrence. To elucidate the role of these cells, we developed LGR5-specific monoclonal antibodies and a high-sensitivity immunofluorescence method to visualize the stem cell marker LGR5 in clinical tumors. Furthermore, we established a unique colorectal cancer cell line, PLR123, which maintains robust stem cell properties, and developed an in vitro model to study tumor recurrence. Through analyses including single-cell RNA sequencing and small molecule screening, we identified the RNA Polymerase I inhibitor BMH-21 as a compound that effectively suppresses recurrence both in vitro and in vivo. This article comprehensively reviews our series of studies on understanding the mechanisms of cancer stem cell-driven resistance and offers insights supporting the development of novel therapies aimed at preventing tumor relapses.</p>

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Molecular analysis of tumor recurrence using established cancer stem cell-line and drug discovery

  • 期刊论文

  • 发表日期：

    2026年1月20日

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  • Kiyotaka Nakano,
  • Eiji Oki,
  • Masaki Yamazaki,
  • Masami Suzuki,
  • Shigeto Kawai,
  • Yoko Zaitsu,
  • Chiyoko Nishime,
  • Koji Ando,
  • Genta Nagae,
  • Norifumi Harimoto,
  • Mitsuhiko Ota,
  • Tetsuro Kawazoe,
  • Kentaro Nonaka,
  • Keita Natsugoe,
  • Sachie Omori,
  • Hiroshi Saeki,
  • Hiroyuki Aburatani,
  • Tatsumi Yamazaki,
  • Yoshihiko Maehara

摘要

Despite advances in adjuvant therapy for colorectal cancer, tumor relapses, often driven by minimal residual disease, remain a formidable clinical challenge. The cancer stem cell hypothesis provides a key framework for understanding this problem, positing that a small, therapy-resistant subpopulation of cells drives recurrence. To elucidate the role of these cells, we developed LGR5-specific monoclonal antibodies and a high-sensitivity immunofluorescence method to visualize the stem cell marker LGR5 in clinical tumors. Furthermore, we established a unique colorectal cancer cell line, PLR123, which maintains robust stem cell properties, and developed an in vitro model to study tumor recurrence. Through analyses including single-cell RNA sequencing and small molecule screening, we identified the RNA Polymerase I inhibitor BMH-21 as a compound that effectively suppresses recurrence both in vitro and in vivo. This article comprehensively reviews our series of studies on understanding the mechanisms of cancer stem cell-driven resistance and offers insights supporting the development of novel therapies aimed at preventing tumor relapses.