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

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.