Tumor organoids: synergistic applications, current challenges, and future prospects in cancer therapy.

Patient-derived cancer cells (PDCs) and patient-derived xenografts (PDXs) are often used as tumor models, but have many shortcomings. PDCs not only lack diversity in terms of cell type, spatial organization, and microenvironment but also have adverse effects in stem cell cultures, whereas PDX are expensive with a low transplantation success rate and require a long culture time. In recent years, advances in three-dimensional (3D) organoid culture technology have led to the development of novel physiological systems that model the tissues of origin more precisely than traditional culture methods. Patient-derived cancer organoids bridge the conventional gaps in PDC and PDX models and closely reflect the pathophysiological features of natural tumorigenesis and metastasis, and have led to new patient-specific drug screening techniques, development of individualized treatment regimens, and discovery of prognostic biomarkers and mechanisms of resistance. Synergistic combinations of cancer organoids with other technologies, for example, organ-on-a-chip, 3D bio-printing, and CRISPR-Cas9-mediated homology-independent organoid transgenesis, and with treatments, such as immunotherapy, have been useful in overcoming their limitations and led to the development of more suitable model systems that recapitulate the complex stroma of cancer, inter-organ and intra-organ communications, and potentially multiorgan metastasis. In this review, we discuss various methods for the creation of organ-specific cancer organoids and summarize organ-specific advances and applications, synergistic technologies, and treatments as well as current limitations and future prospects for cancer organoids. Further advances will bring this novel 3D organoid culture technique closer to clinical practice in the future.

Qu J ，Kalyani FS ，Liu L ，Cheng T ，Chen L ... -  《Cancer Communications》

Emerging organoid models: leaping forward in cancer research.

Fan H ，Demirci U ，Chen P 《Journal of Hematology & Oncology》

Patient-derived organoids as a model for tumor research.

Cancer represents a leading cause of death, despite the rapid progress of cancer research, leading to urgent need for accurate preclinical model to further study of tumor mechanism and accelerate translational applications. Cancer cell lines cannot fully recapitulate tumors of different patients due to the lack of tumor complexity and specification, while the high technical difficulty, long time, and substantial cost of patient-derived xenograft model makes it unable to be used extensively for all types of tumors and large-scale drug screening. Patient-derived organoids can be established rapidly with a high success rate from many tumors, and precisely replicate the key histopathological, genetic, and phenotypic features, as well as therapeutic response of patient tumor. Therefore, they are extensively used in cancer basic research, biobanking, disease modeling and precision medicine. The combinations of cancer organoids with other advanced technologies, such as 3D bio-printing, organ-on-a-chip, and CRISPR-Cas9, contributes to the more complete replication of complex tumor microenvironment and tumorigenesis. In this review, we discuss the various methods of the establishment and the application of patient-derived organoids in diverse tumors as well as the limitations and future prospects of these models. Further advances of tumor organoids are expected to bridge the huge gap between bench and bedside and provide the unprecedented opportunities to advance cancer research.

Wang J ，Feng X ，Li Z ，Chen Y ，Huang W ... -  《-》

Preclinical tumor organoid models in personalized cancer therapy: Not everyone fits the mold.

In contrast to conventional cancer treatment, in personalized cancer medicine each patient receives a specific treatment. The response to therapy, clinical outcomes, and tumor behavior such as metastases, tumor progression, carcinogenesis can be significantly affected by the heterogeneous tumor microenvironment (TME) and interpersonal differences. Therefore, using native tumor microenvironment mimicking models is necessary to improving personalized cancer therapy. Both in vitro 2D cell culture and in vivo animal models poorly recapitulate the heterogeneous tumor (immune) microenvironments of native tumors. The development of 3D culture models, native tumor microenvironment mimicking models, made it possible to evaluate the chemoresistance of tumor tissue and the functionality of drugs in the presence of cell-extracellular matrix and cell-cell interactions in a 3D construction. Various personalized tumor models have been designed to preserving the native tumor microenvironment, including patient-derived tumor xenografts and organoid culture strategies. In this review, we will discuss the patient-derived organoids as a native tumor microenvironment mimicking model in personalized cancer therapy. In addition, we will also review the potential and the limitations of organoid culture systems for predicting patient outcomes and preclinical drug screening. Finally, we will discuss immunotherapy drug screening in tumor organoids by using microfluidic technology.

Hu LF ，Yang X ，Lan HR ，Fang XL ，Chen XY ，Jin KT ... -  《-》

Organoids: An intermediate modeling platform in precision oncology.

Jin MZ ，Han RR ，Qiu GZ ，Ju XC ，Lou G ，Jin WL ... -  《-》