# Biomimetic 3D-Bioprinted organoids of thymic epithelial tumors for translational drug screening and biomarker identification

## TL;DR

Researchers created 3D-printed tumor models of thymic epithelial tumors to test drugs and identify biomarkers for better treatment.

## Contribution

The first 3D bioprinted organoid model of thymic epithelial tumors using proteomic data to guide biomaterial design.

## Key findings

- 3D-bioprinted organoids better replicate tumor properties than traditional Matrigel models.
- Lurbinectedin was identified as a potent therapeutic candidate for thymic epithelial tumors.
- PBX3, REPS2, and CXCR4 are potential biomarkers for treatment efficacy.

## Abstract

Thymic epithelial tumors (TETs), including thymic carcinoma and thymoma, are rare malignancies lacking both effective therapies and validated biomarkers to guide treatment. Here, we report the first 3D (three-dimensional) bioprinted organoid model of TETs, established through a proteomic data-driven biomaterial design strategy. Patient tumor tissues were first decellularized and analyzed by proteomics to determine their extracellular matrix (ECM) composition. The results revealed distributions of ECM proteins which guided the formulation of photocurable bioinks. The resulting 3D-bioprinted organoids supported primary TET cell proliferation, and more faithfully replicated the biophysical properties and molecular characteristics of native tumors than traditional Matrigel-cultured organoids. Leveraging this biomimetic platform, we conducted high-throughput drug screening and identified lurbinectedin as a potent therapeutic candidate for TETs. Transcriptomic profiling revealed its anti-TET mechanism. Integrating RNAseq data with TCGA survival analysis further identified PBX3, REPS2, and CXCR4 as potential efficacy-predictive biomarkers. This study establishes a translational framework linking 3D bioprinted TET models with biomarker discovery, offering a standardized platform for precision drug screening and mechanistic exploration in thymic epithelial tumors.

Image 1