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Transforming cancer treatment: integrating patient-derived organoids and CRISPR screening for precision medicine

Ziyi Zhu1,2, Jiayang Shen1,2, Paul Chi-Lui Ho3

  • 1The First Affiliated Hospital of Yangtze University, Yangtze University, Jingzhou, Hubei, China.

Frontiers in Pharmacology
|April 9, 2025
PubMed

Insights

Patient-derived organoids (PDOs) combined with CRISPR gene editing offer a powerful preclinical cancer research model. This approach accelerates the discovery of new cancer therapies and improves understanding of tumor biology for precision oncology.

Area of Science:

  • Oncology
  • Genomics
  • Biotechnology

Background:

  • High cancer mortality necessitates novel therapeutic strategies and deeper tumor biology insights.
  • Patient-derived organoids (PDOs) are advanced preclinical models mirroring primary tumor complexity.
  • CRISPR technology enables precise genetic manipulation for functional genomics.

Purpose of the Study:

  • To review recent progress in CRISPR-based functional screens using PDOs for cancer research.
  • To explore the application of PDOs and CRISPR in modeling the tumor microenvironment (TME).
  • To highlight the synergy of PDOs and CRISPR in advancing cancer immunotherapy and precision oncology.

Main Methods:

  • Leveraging CRISPR-mediated functional screens within patient-derived organoids (PDOs).
  • Utilizing PDOs for high-throughput functional genomics across various cancer types.
  • Integrating PDOs with CRISPR screens to model tumor microenvironment (TME) interactions.

Main Results:

  • CRISPR screens in PDOs effectively identify cancer driver genes and therapeutic targets.
  • PDO-CRISPR platforms facilitate detailed tumor microenvironment (TME) modeling.
  • Combined approaches reveal immune evasion mechanisms and enhance immunotherapy strategies.

Conclusions:

  • The integration of PDOs and CRISPR screens represents a significant advancement in preclinical cancer research.
  • This powerful combination accelerates the identification of novel therapeutic targets and biomarkers.
  • These technologies hold substantial promise for the future of precision oncology and improved cancer patient outcomes.
Keywords:
CRISPR screeningcancer treatmentimmunotherapypatient-derived organoidsprecision medicine

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