Personalizing Cancer Treatments Empirically in the Laboratory: Patient-Specific Tumor Organoids for Optimizing Precision Medicine
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Purpose of Review
Cancer is often a complicated and dynamic disease, which makes determining the optimal treatment for a given patient a difficult endeavor. Moreover, even within a particular cancer type, different patients often have varying responses to the same therapies. Bioengineered tumor model systems specific to patients would allow preemptive screening of personalized therapies, facilitating identification of the most effective treatments prior to administration in the patients. Here, we provide an overview of organoid technology, and how these bioengineered tumor models can be harnessed for patient-centric personalized oncology.
Organoid models have ranged from simple cell spheroids to more complex tumor-on-a-chip systems. The earliest of these models were comprised of easy to culture cell lines, but recent advances in 3D cell culture approaches have facilitated generation of human primary cell-based organoids. Importantly, recent efforts have been made to employ tumor biospecimens from human patients to create personalized tumor models for patient-specific predictive drug screening.
Bioengineering and tissue engineering technologies have advanced significantly in recent years, culminating in the capability to biofabricate tissue and tumor organoids derived from individual human patients. In the near future, we anticipate such models being implemented in parallel with clinical practice as patient-oriented screening tools, thereby improving the success rates of oncology.
KeywordsPrecision medicine Personalized medicine Tumor organoids Biofabrication Tissue engineering
Compliance with Ethical Standards
Conflict of Interest
Andrea Mazzocchi and Konstantinos Votanopoulos declare that they have no conflict of interest.
Aleksander Skardal reports a pending patent on cancer modeling platforms and methods of using the same.
Human and Animal Rights and Informed Consent
This article does not contain any studies with human or animal subjects performed by any of the authors.
Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance
- 8.• Zhang YS, Aleman J, Shin SR, Kilic T, Kim D, Mousavi Shaegh SA, et al. Multisensor-integrated organs-on-chips platform for automated and continual in situ monitoring of organoid behaviors. Proc Natl Acad Sci U S A. 2017;114(12):E2293–E302. This study describes organ-on-a-chip devices with a sophisticated biosensor suite that allows automated and real-time sensing of organoid health and behaviors CrossRefPubMedPubMedCentralGoogle Scholar
- 9.• Skardal A, Murphy SV, Devarasetty M, Mead I, Kang HW, Seol YJ, et al. Multi-tissue interactions in an integrated three-tissue organ-on-a-chip platform. Sci Rep. 2017;7(1):8837. This study demonstrates the development and implementation of multiple human organoids in a single perfused “body-on-a-chip” platform and showcases several integrated drug studies in which the function of one organoid type influences outcomes of the other organoid types CrossRefPubMedPubMedCentralGoogle Scholar
- 26.Skardal A. Bioprinting essentials of cell and protein viability. In: Atala A, Yoo JJ, editors. Essentials of 3D Biofabrication and Translation: Elsevier; 2015.Google Scholar
- 35.•• Mazzocchi AR, Rajan SAP, Votanopoulos KI, Hall AR, Skardal A. In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening. Sci Rep. 2018;8(1):2886. This study describes biofabrication of tumor organoids and tumor-on-a-chip devices using actual patient tumor-derived biospecimens, and subsequent drug screening studies that correlate with patient drug responses. Google Scholar
- 42.Usta OB, McCarty WJ, Bale S, Hegde M, Jindal R, Bhushan A, et al. Microengineered cell and tissue systems for drug screening and toxicology applications: evolution of in-vitro liver technologies. Technology (Singap World Sci). 2015;3(1):1–26.Google Scholar
- 43.Mazzocchi AR, Soker S, Skardal A. Biofabrication technologies for developing in vitro tumor models. In: Soker S, Skardal a, editors. Tumor organoids. Berlin, Germany: Springer Nature; 2017.Google Scholar