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 ... -  《-》

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》

Applications of lung cancer organoids in precision medicine: from bench to bedside.

Li H ，Chen Z ，Chen N ，Fan Y ，Xu Y ，Xu X ... -  《Cell Communication and Signaling》

Organoids: An intermediate modeling platform in precision oncology.

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

Complex in vitro 3D models of digestive system tumors to advance precision medicine and drug testing: Progress, challenges, and trends.

Digestive system cancers account for nearly half of all cancers around the world and have a high mortality rate. Cell culture and animal models represent cornerstones of digestive cancer research. However, their ability to enable cancer precision medicine is limited. Cell culture models cannot retain the genetic and phenotypic heterogeneity of tumors and lack tumor microenvironment (TME). Patient-derived xenograft mouse models are not suitable for immune-oncology research. While humanized mouse models are time- and cost-consuming. Suitable preclinical models, which can facilitate the understanding of mechanisms of tumor progression and develop new therapeutic strategies, are in high demand. This review article summarizes the recent progress on the establishment of TME by using tumor organoid models and microfluidic systems. The main challenges regarding the translation of organoid models from bench to bedside are discussed. The integration of organoids and a microfluidic platform is the emerging trend in drug screening and precision medicine. A future prospective on this field is also provided.

Song SL ，Li B ，Carvalho MR ，Wang HJ ，Mao DL ，Wei JT ，Chen W ，Weng ZH ，Chen YC ，Deng CX ，Reis RL ，Oliveira JM ，He YL ，Yan LP ，Zhang CH ... -  《-》