Tumoroids are the result of developments in cell culture towards three dimensional (3D) models that overcome the inability of two-dimensional (2D) monolayer cell cultures to imitate many aspects of tissue architecture and microenvironments [1]. These 3D models include organoids that can be defined as a complex, self-organized cell aggregate derived from primary tissue or mesenchymal stem cells (MSCs).
are capable of self-renewal, typically organized in 3D constructs able to replicate the complex structure of an organ and mimic its’ in vivo physiology [2].
are essentially “tumor-like organoids” that are typically prepared using cells from primary tumors harvested from patients.
3D tumor models, or tumoroids, have many advantages over 2D models [3], including:
Overall, 3D cell-cultures increase the dimensionality of cell-cell interactions that are fundamental to generating a phenotype predictive of in vivo biology but performed in vitro [4]. As such tumoroids can mimic, or recapitulate, the human tumor microenvironment and are therefore a better predictive tool for drug discovery compared to 2D models [5].
Since tumoroids can recapitulate the complex genetic and molecular compositions of solid cancers, they are extremely valuable in preclinical research, the study of disease progression, the identification of drug targets, and drug testing in general [6,7,8]. At the level of the individual, a tumoroid based on a patient’s tumor cells can be used in personalized medicine for the cost and time effective prediction of drug response of specific tumors.
A series of proof-of-concept studies demonstrates the potential for high-resolution image-based analysis of 3D tumoroid models for drug discovery applications that could soon become routine practice in drug discovery workflows [9]. The studies included studying real-time immune cell interactions in a multicellular 3D lung cancer model and using a 3D model of gastric carcinoma in a high-throughput screening application to determine dose-dependent drug efficacy.
This study examines factors affecting human glioblastoma angiogenesis and shows the power of tumoroids in mimicking complex tumor microenvironments [10]. The model is scalable, easy to control, cost-effective and can be used as a preclinical model to study microenvironment cues of tumor angiogenesis.
Patient-derived xenograft (PDX) models are effective preclinical models, but their cost and laborious preparation limits their value as platforms for high-throughput drug screens [11]. A PDXEx model was generated by isolating cells released from a PDX tumor harvested from a mouse, coating them with NanoShuttle-PL (Greiner Bio-One), and maintaining the cells in a levitated state before magnetic 3D bioprinting, resulting in a cost and time efficient in vitro first-pass drug screening platform.
The value of tumoroids in personalized medicine is illustrated by a study on lung cancer [12]. This cancer form shows substantial genetic and phenotypic heterogeneity across individuals, making it particularly interesting as a target for personalized medicine. Tumoroids and normal bronchial organoids were quickly established from patient tissues and recapitulated the original tissue architecture and genomic alterations even after extensive in vitro expansion. The tumoroids also responded to drugs based on their genomic alterations, making them a powerful tool for predicting patient-specific drug responses.
To summarize, tumoroids are highly translational tools that can recapitulate the complex genetic and molecular compositions of solid cancers. They have a phenotype that is predictive of in vivo biology, down to the level of an individual primary tumor in a patient, if necessary, but can be maintained and analyzed in vitro. Tumoroids can therefore be used to accelerate the identification of drug targets, streamline drug testing, and predict drug response in personalized medicine.
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