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Genomic and Single-Cell Analyses Characterize Patient-Derived Tumor Organoids to Enable Personalized Therapy for Head

Jung Hyun Um1, Yueyuan Zheng2, Qiong Mao2,3

  • 1Department of Otorhinolaryngology, Yonsei University College of Medicine, Seoul, Korea.

Cancer Research
|April 22, 2025
PubMed

Insights

Patient-derived organoids (PDOs) from head and neck squamous cell carcinoma (HNSCC) models mimic tumor traits and predict cisplatin response. A hybrid epithelial-mesenchymal transition (hEMT) program and amphiregulin (AREG) drive resistance.

Area of Science:

  • Oncology
  • Genomics
  • Translational Medicine

Background:

  • Head and neck squamous cell carcinoma (HNSCC) presents challenges due to tumor heterogeneity and treatment resistance.
  • Improved biological understanding and targeted therapies are crucial for HNSCC management.

Purpose of the Study:

  • To establish and validate patient-derived tumor organoids (PDOs) as reliable models for HNSCC research.
  • To investigate intratumor heterogeneity (ITH) and its association with treatment response in HNSCC.
  • To identify potential therapeutic targets for personalized HNSCC treatment.

Main Methods:

  • Establishment and long-term culture of 31 HNSCC patient-derived tumor organoids (PDOs).
  • Assessment of genomic and histopathological feature preservation in PDOs.
  • Ex vivo drug sensitivity testing (cisplatin) and correlation with patient outcomes.
  • Bulk and single-cell RNA sequencing to analyze molecular subtypes and ITH.
  • Functional analyses to identify regulators of hybrid epithelial-mesenchymal transition (hEMT) and drug resistance.

Main Results:

  • PDOs faithfully recapitulated the genomic and histopathological characteristics of primary HNSCC tumors.
  • Ex vivo cisplatin sensitivity of PDOs accurately predicted patient treatment responses.
  • Single-cell RNA sequencing revealed molecular subtypes and ITH within PDOs, mirroring patient tumors.
  • A hybrid epithelial-mesenchymal transition (hEMT)-like ITH program correlated with cisplatin resistance and poorer patient survival.
  • Amphiregulin (AREG) was identified as a key regulator of the hEMT state and contributed to cisplatin resistance via EGFR pathway activation.

Conclusions:

  • HNSCC PDOs are robust and versatile models for studying tumor biology and treatment response.
  • PDOs provide predictive insights into ITH programs, aiding in the understanding of treatment resistance.
  • The study identified AREG and its role in hEMT as a potential therapeutic target for personalized HNSCC medicine.

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