What is a Tumoroid?
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).
Organoids
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].
Tumoroids
are essentially “tumor-like organoids” that are typically prepared using cells from primary tumors harvested from patients.
Why use tumoroids?
3D tumor models, or tumoroids, have many advantages over 2D models [3], including:
- The natural cell morphology is preserved, and cells grow into multiple layers
- The 3D form mimics the access to nutrients in tumors, with core cells often inactive
- Cells are differentiated
- Cell junctions are common
- 3D models are generally more resistant to drugs, reducing the number of false positive results
- Cell proliferation rates are in vivo-like
- Gene and protein expression levels resemble those of cells in vivo
- Levels of resistance to drug-induced apoptosis are higher
- Cells can respond more realistically to mechanical stimuli
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].
What are tumoroids used for?
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.
Examples of the use of tumoroids
Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening
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.
A vascularized tumoroid model for human glioblastoma angiogenesis
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.
Replacing the PDX model with a rapid and cost-effective high-throughput first-pass screening platform
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.
Disease modeling with 3D cell-based assays using a novel flowchip system and high-content imaging
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.
Tumoroids – a highly translational tool
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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References
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[8] Tatullo M, Marrelli B, Benincasa C, Aiello E, Makeeva I, Zavan B, Ballini A, De Vito D, Spagnuolo G. Organoids in Translational Oncology. J Clin Med. 2020 Aug 27;9(9):2774. doi: 10.3390/jcm9092774. PMID: 32867142; PMCID: PMC7564148.
[9] Kim M, Mun H, Sung CO, Cho EJ, Jeon HJ, Chun SM, Jung DJ, Shin TH, Jeong GS, Kim DK, Choi EK, Jeong SY, Taylor AM, Jain S, Meyerson M, Jang SJ. Patient-derived lung cancer organoids as in vitro cancer models for therapeutic screening. Nat Commun. 2019 Sep 5;10(1):3991. doi: 10.1038/s41467-019-11867-6. PMID: 31488816; PMCID: PMC6728380.
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[11] Eckhardt BL, Gagliardi M, Iles L, Evans K, Ivan C, Liu X, Liu CG, Souza G, Rao A, Meric-Bernstam F, Ueno NT, Bartholomeusz GA. Clinically relevant inflammatory breast cancer patient-derived xenograft-derived ex vivo model for evaluation of tumor-specific therapies. PLoS One. 2018 May 16;13(5):e0195932. doi: 10.1371/journal.pone.0195932. PMID: 29768500; PMCID: PMC5955489.
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