Exploring clinically anchored therapeutic stratification and tumor-stroma heterogeneity using patient-derived 3D bioprinted primary liver cancer models.

@article{zhang2026exploring,
  title = {{Exploring clinically anchored therapeutic stratification and tumor-stroma heterogeneity using patient-derived 3D bioprinted primary liver cancer models.}},
  author = {Kai Zhang and Liwei Du and Minghao Sun and Yuce Lu and Mingchang Pang and Shangze Jiang and Xiyue Liu and Jiaxun Dong and Bao Jin and Fu Xu and Hang Sun and Jiangang Zhang and Huiyu Yang and Xinting Sang and Shunda Du and Haitao Zhao and Haifeng Xu and Yilei Mao and Huayu Yang},
  journal = {Molecular cancer},
  year = {2026},
  month = jul,
  doi = {10.1186/s12943-026-02751-1},
  url = {https://europepmc.org/article/MED/42928279},
  note = {CC BY-NC-ND},
}

TY  - JOUR
TI  - Exploring clinically anchored therapeutic stratification and tumor-stroma heterogeneity using patient-derived 3D bioprinted primary liver cancer models.
AU  - Kai Zhang
AU  - Liwei Du
AU  - Minghao Sun
AU  - Yuce Lu
AU  - Mingchang Pang
AU  - Shangze Jiang
AU  - Xiyue Liu
AU  - Jiaxun Dong
AU  - Bao Jin
AU  - Fu Xu
AU  - Hang Sun
AU  - Jiangang Zhang
AU  - Huiyu Yang
AU  - Xinting Sang
AU  - Shunda Du
AU  - Haitao Zhao
AU  - Haifeng Xu
AU  - Yilei Mao
AU  - Huayu Yang
PY  - 2026
DA  - 2026/07/28
JO  - Molecular cancer
DO  - 10.1186/s12943-026-02751-1
UR  - https://europepmc.org/article/MED/42928279
AB  - Background  The marked heterogeneity of primary liver cancer (PLC), together with the dynamic influence of the tumor microenvironment (TME), remains a major challenge to precision oncology. As currently available therapies provide limited benefit for many patients and robust preclinical platforms for rapid, patient-specific treatment stratification are lacking, there is an urgent need for models that faithfully preserve individual tumor architecture and cellular diversity.Methods  We established three-dimensional bioprinted primary liver cancer (3DP-PLC) models comprising 61 patient-derived monocultures and 34 co-culture models with patient-matched cancer-associated fibroblasts (CAFs). To explore the correlation between ex vivo models and clinical drug response, we developed a clinically anchored hybrid stratification framework for response classification. In parallel, the 3DP-PLC/CAF co-culture biobank was used to investigate stromal regulation of therapeutic response.Results  These 3DP-PLC constructs preserved the histological features, biomarker expression patterns, mutational landscapes, and transcriptomic profiles of their corresponding parental tumors. Drug-sensitivity profiling across the biobank revealed substantial intertumoral heterogeneity in therapeutic responses. The clinically anchored hybrid stratification framework integrating ex vivo pharmaceutical profiles with external clinical benchmark data enabled interpretable response classification and demonstrated clinical relevance in patients receiving neoadjuvant or adjuvant targeted therapy. In parallel, the 3DP-PLC/CAF co-culture biobank, combined with single-cell transcriptomic analysis, recapitulated fibrous ring-like architecture and revealed CAF-associated drug-resistant states.Conclusions  These findings support 3DP-PLC as a high-fidelity and scalable platform for personalized therapeutic stratification and mechanistic investigation of tumor-stroma interactions in PLC.
SN  - 1476-4598
ER  -