Organoids: approaches and utility in cancer research.

Organoids are three-dimensional cellular structures with self-organizing and self-differentiation capacities. They faithfully recapitulate structures and functions of in vivo organs as represented by functionality and microstructural definitions. Heterogeneity in in vitro disease modeling is one of the main reasons for anti-cancer therapy failures. Establishing a powerful model to represent tumor heterogeneity is crucial for elucidating tumor biology and developing effective therapeutic strategies. Tumor organoids can retain the original tumor heterogeneity and are commonly used to mimic the cancer microenvironment when co-cultured with fibroblasts and immune cells; therefore, considerable effort has been made recently to promote the use of this new technology from basic research to clinical studies in tumors. In combination with gene editing technology and microfluidic chip systems, engineered tumor organoids show promising abilities to recapitulate tumorigenesis and metastasis. In many studies, the responses of tumor organoids to various drugs have shown a positive correlation with patient responses. Owing to these consistent responses and personalized characteristics with patient data, tumor organoids show excellent potential for preclinical research. Here, we summarize the properties of different tumor models and review their current state and progress in tumor organoids. We further discuss the substantial challenges and prospects in the rapidly developing tumor organoid field.

Zhou B ，Feng Z ，Xu J ，Xie J ... -  《-》

Cancer modeling meets human organoid technology.

Organoids are microscopic self-organizing, three-dimensional structures that are grown from stem cells in vitro. They recapitulate many structural and functional aspects of their in vivo counterpart organs. This versatile technology has led to the development of many novel human cancer models. It is now possible to create indefinitely expanding organoids starting from tumor tissue of individuals suffering from a range of carcinomas. Alternatively, CRISPR-based gene modification allows the engineering of organoid models of cancer through the introduction of any combination of cancer gene alterations to normal organoids. When combined with immune cells and fibroblasts, tumor organoids become models for the cancer microenvironment enabling immune-oncology applications. Emerging evidence indicates that organoids can be used to accurately predict drug responses in a personalized treatment setting. Here, we review the current state and future prospects of the rapidly evolving tumor organoid field.

Tuveson D ，Clevers H 《-》

Emerging organoid models: leaping forward in cancer research.

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

Reconstructing the tumor architecture into organoids.

Cancer remains a leading health burden worldwide. One of the challenges hindering cancer therapy development is the substantial discrepancies between the existing cancer models and the tumor microenvironment (TME) of human patients. Constructing tumor organoids represents an emerging approach to recapitulate the pathophysiological features of the TME in vitro. Over the past decade, various approaches have been demonstrated to engineer tumor organoids as in vitro cancer models, such as incorporating multiple cellular populations, reconstructing biophysical and chemical traits, and even recapitulating structural features. In this review, we focus on engineering approaches for building tumor organoids, including biomaterial-based, microfabrication-assisted, and synthetic biology-facilitated strategies. Furthermore, we summarize the applications of engineered tumor organoids in basic cancer research, cancer drug discovery, and personalized medicine. We also discuss the challenges and future opportunities in using tumor organoids for broader applications.

Luo Z ，Zhou X ，Mandal K ，He N ，Wennerberg W ，Qu M ，Jiang X ，Sun W ，Khademhosseini A ... -  《-》

Tumor organoids: applications in cancer modeling and potentials in precision medicine.

Cancer is a top-ranked life-threatening disease with intratumor heterogeneity. Tumor heterogeneity is associated with metastasis, relapse, and therapy resistance. These factors contribute to treatment failure and an unfavorable prognosis. Personalized tumor models faithfully capturing the tumor heterogeneity of individual patients are urgently needed for precision medicine. Advances in stem cell culture have given rise to powerful organoid technology for the generation of in vitro three-dimensional tissues that have been shown to more accurately recapitulate the structures, specific functions, molecular characteristics, genomic alterations, expression profiles, and tumor microenvironment of primary tumors. Tumoroids in vitro serve as an important component of the pipeline for the discovery of potential therapeutic targets and the identification of novel compounds. In this review, we will summarize recent advances in tumoroid cultures as an excellent tool for accurate cancer modeling. Additionally, vascularization and immune microenvironment modeling based on organoid technology will also be described. Furthermore, we will summarize the great potential of tumor organoids in predicting the therapeutic response, investigating resistance-related mechanisms, optimizing treatment strategies, and exploring potential therapies. In addition, the bottlenecks and challenges of current tumoroids will also be discussed in this review.

Xu H ，Jiao D ，Liu A ，Wu K ... -  《Journal of Hematology & Oncology》