Scholarlink

Background <p>Colorectal cancer (CRC) exhibits pronounced inter- and intratumoral heterogeneity, emphasizing the need for preclinical models that accurately capture its molecular and histological diversity. Patient-derived organoids (PDOs) represent valuable ex vivo systems to model CRC, yet whether they can preserve subtype-specific features and maintain fidelity upon in vivo transplantation remains unclear.</p> Methods <p>We established a biobank of PDOs from both treatment-naïve and neoadjuvant-treated CRC patients, encompassing the major histological subtypes – micropapillary, medullary, serrated, mucinous, and adenocarcinoma not otherwise specified (NOS). PDOs were comprehensively characterized by histomorphological, genomic, and transcriptomic analyses. To assess in vivo fidelity, PDOs were orthotopically transplanted into immunodeficient mice to generate patient-derived organoid xenografts (PDOXs). PDOX-derived tumors and organoids were analyzed to evaluate the preservation of histological and molecular traits, as well as therapy responses.</p> Results <p>PDOs displayed distinct, subtype-specific morphologies and growth patterns that closely paralleled their respective patient tumor histologies. Orthotopic PDOXs recapitulated the histological architecture, gene expression profiles, and signaling pathway activation of the original tumors. PDOX-derived organoids retained these subtype-specific morphologies, molecular features, and exhibited similar responses to FOLFOX treatment as their corresponding PDOs, confirming both molecular and functional stability of the organoid-xenograft cycle.</p> Conclusion <p>This study establishes orthotopic transplantation of CRC PDOs as a robust and predictive preclinical model that captures the full spectrum of CRC heterogeneity. The model preserves histological and molecular subtype fidelity across in vitro and in vivo contexts and enables functional assessment of therapy response. By bridging patient-derived tumor biology with translational modeling, this platform provides a valuable resource for dissecting CRC pathogenesis and advancing patient-tailored precision oncology.</p> Graphical Abstract <p></p>

错误：搜索内容不能为空，请输入英文关键词
错误：关键词超出字数限制，请精简
高级检索

A translational colorectal cancer organoid biobank mirrors patients’ tumor histology, molecular profiles, and treatment responses

  • 期刊论文

  • 出版模式：

    开放获取

  • 发表日期：

    2026年2月25日

查看全文
  • Moritz Jesinghaus,
  • Miguel Gomes Silva,
  • Antonio Enrico Zaurito,
  • Valentina Brunner,
  • Frederic Saab,
  • Anantharamanan Rajamani,
  • Niklas de Andrade Krätzig,
  • Nicholas Bodenstein,
  • Rémi Guillemant,
  • Junika Pohl,
  • Maxime Schmitt,
  • Rupert Öllinger,
  • Federico Fusco,
  • Julius Shakhtour,
  • Peter Klare,
  • Klaus-Peter Janssen,
  • Sebastian Foersch,
  • Katja Steiger,
  • Roland Rad,
  • Nicole Pfarr,
  • Dieter Saur,
  • Markus Tschurtschenthaler

摘要

Background

Colorectal cancer (CRC) exhibits pronounced inter- and intratumoral heterogeneity, emphasizing the need for preclinical models that accurately capture its molecular and histological diversity. Patient-derived organoids (PDOs) represent valuable ex vivo systems to model CRC, yet whether they can preserve subtype-specific features and maintain fidelity upon in vivo transplantation remains unclear.

Methods

We established a biobank of PDOs from both treatment-naïve and neoadjuvant-treated CRC patients, encompassing the major histological subtypes – micropapillary, medullary, serrated, mucinous, and adenocarcinoma not otherwise specified (NOS). PDOs were comprehensively characterized by histomorphological, genomic, and transcriptomic analyses. To assess in vivo fidelity, PDOs were orthotopically transplanted into immunodeficient mice to generate patient-derived organoid xenografts (PDOXs). PDOX-derived tumors and organoids were analyzed to evaluate the preservation of histological and molecular traits, as well as therapy responses.

Results

PDOs displayed distinct, subtype-specific morphologies and growth patterns that closely paralleled their respective patient tumor histologies. Orthotopic PDOXs recapitulated the histological architecture, gene expression profiles, and signaling pathway activation of the original tumors. PDOX-derived organoids retained these subtype-specific morphologies, molecular features, and exhibited similar responses to FOLFOX treatment as their corresponding PDOs, confirming both molecular and functional stability of the organoid-xenograft cycle.

Conclusion

This study establishes orthotopic transplantation of CRC PDOs as a robust and predictive preclinical model that captures the full spectrum of CRC heterogeneity. The model preserves histological and molecular subtype fidelity across in vitro and in vivo contexts and enables functional assessment of therapy response. By bridging patient-derived tumor biology with translational modeling, this platform provides a valuable resource for dissecting CRC pathogenesis and advancing patient-tailored precision oncology.

Graphical Abstract