Traditional tumor models cannot perfectly simulate the real state of tumors in vivo, resulting in the termination of many clinical trials. 3D tumor models’ technology provides new in vitro models that bridge the gap between in vitro and in vivo findings, and organoids maintain the properties of the original tissue over a long period of culture, which enables extensive research in this area. In addition, they can be used as a substitute for animal and in vitro models, and organoids can be established from patients’ normal and malignant tissues, with unique advantages in clinical drug development and in guiding individualized therapies. 3D tumor models also provide a promising platform for high-throughput research, drug and toxicity testing, disease modeling, and regenerative medicine. This report summarizes the 3D tumor model, including evidence regarding the 3D tumor cell culture model, 3D tumor slice model, and organoid culture model. In addition, it provides evidence regarding the application of 3D tumor organoid models in precision oncology and drug screening. The aim of this report is to elucidate the value of 3D tumor models in cancer research and provide a preclinical reference for the precise treatment of cancer patients.

/pdf/advances-in-the-application-of-3d-tumor-models-in-precision-2mkj82bc.pdf

Advances in the application of 3D tumor models in precision oncology and drug screening

Targeting cancer drug resistance utilizing organoid technology.

Patient-derived organoids (PDOs) have emerged as a promising platform for clinical and translational studies.A strong correlation exists between clinical outcomes and the use of PDOs to predict the efficacy of chemotherapy and/or radiotherapy.To standardize interpretation and enhance scientific communication in the field of cancer precision medicine, we revisit the concept of PDO-based drug sensitivity testing (DST).We present an expert consensus-driven approach for medication selection aimed at predicting patient responses.To further standardize PDO-based DST, we propose guidelines for clarification and characterization.Additionally, we identify several major challenges in clinical prediction when utilizing PDOs. 

pdf/building-consensus-on-the-application-of-organoid-based-drug-4o891ucx3o.pdf

Building consensus on the application of organoid-based drug sensitivity testing in cancer precision medicine and drug development

Abstract Recent development of human three-dimensional organoid cultures has opened new doors and opportunities ranging from modelling human development in vitro to personalised cancer therapies. These new in vitro systems are opening new horizons to the classic understanding of human development and disease. However, the complexity and heterogeneity of these models requires cutting-edge techniques to capture and trace global changes in gene expression to enable identification of key players and uncover the underlying molecular mechanisms. Rapid development of sequencing approaches made possible global transcriptome analyses and epigenetic profiling. Despite challenges in organoid culture and handling, these techniques are now being adapted to embrace organoids derived from a wide range of human tissues. Here, we review current state-of-the-art multi-omics technologies, such as single-cell transcriptomics and chromatin accessibility assays, employed to study organoids as a model for development and a platform for precision medicine. 

/pdf/gene-expression-in-organoids-an-expanding-horizon-3asde12z.pdf

Gene expression in organoids: an expanding horizon

Giant cell-rich lesions of bone represent a heterogeneous group of entities which classically include giant cell tumor of bone, aneurysmal bone cyst, nonossifying fibroma, and Brown tumor of hyperparathyroidism. A recently described subset of giant cell-rich tumors involving bone and soft tissue has been characterized by recurrent HMGA2::NCOR2 fusions and keratin expression. The overlapping clinical, radiographic, and morphological features of these giant cell-rich lesions provide a unique diagnostic challenge, particularly on biopsy. We present 2 additional cases of keratin-positive giant cell-rich tumor of bone with HMGA2::NCOR2 fusions, including 1 patient who developed metastatic disease.

Keratin-Positive Giant Cell-Rich Tumor of Bone Harboring an HMGA2::NCOR2 Fusion: Two Cases, Including a Patient With Metastatic Disease, and Review of the Literature.

Resistance to antitumor treatment contributes to patient mortality. Functional proteomic screening of organoids derived from chemotherapy-treated patients with breast cancer identified nuclear receptor corepressor 2 (NCOR2) histone deacetylase as an inhibitor of cytotoxic stress response and antitumor immunity. High NCOR2 in the tumors of patients with breast cancer predicted chemotherapy refractoriness, tumor recurrence and poor prognosis. Molecular studies revealed that NCOR2 inhibits antitumor treatment by regulating histone deacetylase 3 (HDAC3) to repress interferon regulatory factor 1 (IRF-1)-dependent gene expression and interferon (IFN) signaling. Reducing NCOR2 or impeding its epigenetic activity by modifying its interaction with HDAC3 enhanced chemotherapy responsiveness and restored antitumor immunity. An adeno-associated viral NCOR2-HDAC3 competitor potentiated chemotherapy and immune checkpoint therapy in culture and in vivo by permitting transcription of IRF-1-regulated proapoptosis and inflammatory genes to increase IFN-γ signaling. The findings illustrate the utility of patient-derived organoids for drug discovery and suggest that targeting stress and inflammatory-repressor complexes such as NCOR2-HDAC3 could overcome treatment resistance and improve the outcome of patients with cancer. 

Breast cancer patient-derived organoid screening implicates the repressor NCOR2 in cytotoxic stress response and anti-tumor immunity

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Breast cancer patient-derived organoid screening implicates the repressor NCOR2 in cytotoxic stress response and anti-tumor immunity