Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery

Weeber, Fleur; Ooft, Salo; Dijkstra, Krijn K.; Voest, Emile E.

doi:10.1016/j.chembiol.2017.06.012

Cited by 419 publications

(343 citation statements)

References 62 publications

(125 reference statements)

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“…We next showed that tumor AOs can be used for drug screening (Weeber et al, 2017). As shown in Fig 3D, individual tumor AOs varied greatly in their respective responses in line with their mutational profile.…”

Section: Generation and Characterization Of Human Airway Organoidsmentioning

confidence: 82%

Long‐term expanding human airway organoids for disease modeling

et al. 2019

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Organoids are self‐organizing 3D structures grown from stem cells that recapitulate essential aspects of organ structure and function. Here, we describe a method to establish long‐term‐expanding human airway organoids from broncho‐alveolar resections or lavage material. The pseudostratified airway organoids consist of basal cells, functional multi‐ciliated cells, mucus‐producing secretory cells, and CC10‐secreting club cells. Airway organoids derived from cystic fibrosis (CF) patients allow assessment of CFTR function in an organoid swelling assay. Organoids established from lung cancer resections and metastasis biopsies retain tumor histopathology as well as cancer gene mutations and are amenable to drug screening. Respiratory syncytial virus (RSV) infection recapitulates central disease features, dramatically increases organoid cell motility via the non‐structural viral NS2 protein, and preferentially recruits neutrophils upon co‐culturing. We conclude that human airway organoids represent versatile models for the in vitro study of hereditary, malignant, and infectious pulmonary disease.

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Section: Generation and Characterization Of Human Airway Organoidsmentioning

confidence: 82%

Long‐term expanding human airway organoids for disease modeling

et al. 2019

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“…Furthermore, these patient-derived spheroids can be used to establish large and well-characterized biobanks that comprise the entire spectrum of molecular subtypes comprising the tumor and, subsequently, perform drug screens toward a more personalized and effective therapeutics (Pauli et al, 2017;Weeber, Ooft, Dijkstra, & Voest, 2017).…”

Section: Future Directionsmentioning

confidence: 99%

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

Nunes

Barros

Costa

et al. 2018

Biotech & Bioengineering

541

445

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Three-dimensional cell culture models, such as spheroids, can be used in the process of the development of new anticancer agents because they are able to closely mimic the main features of human solid tumors, namely their structural organization, cellular layered assembling, hypoxia, and nutrient gradients. These properties imprint to the spheroids an anticancer therapeutics resistance profile, which is similar to that displayed by human solid tumors. In this review, an overview of the drug resistance mechanisms observed in 3D tumor spheroids is provided. Furthermore, comparisons between the therapeutics resistance profile exhibited by spheroids, and 2D cell cultures are presented. Finally, examples of the therapeutic approaches that have been developed to surpass the drug resistance mechanisms exhibited by spheroids are described. HIGHLIGHTS•The suitability of 3D cell culture models for drug screening purposes is highlighted. •Spheroids and in vivo human solid tumors structural and functional similarities are emphasized.•The drug resistance mechanisms exhibited by spheroids are described.•Therapeutic approaches used to surpass spheroids' drug resistance mechanisms are described. K E Y W O R D Sdrug resistance, drugs, in vitro models, solid tumors, spheroids

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“…To study therapeutic models in cancer research, 3D organoid models of ductal pancreatic cancers have provided a new spectrum of models of tumor progression by forming neoplasms that proceed to form invasive and metastatic carcinomas [210]. The organoid methodology is a useful system that can be used to identify the characteristics of malignancy, and the creation of complete tissues or neoplastic cancer organoids in vitro might provide better models of cancers in the future [35, 211–214]. Moreover, the CRISPR/Cas9 approach is believed to be a new breakthrough technology that can be used to correct cancer genomes for clinical applications [214].…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

“…The organoid methodology is a useful system that can be used to identify the characteristics of malignancy, and the creation of complete tissues or neoplastic cancer organoids in vitro might provide better models of cancers in the future [35, 211–214]. Moreover, the CRISPR/Cas9 approach is believed to be a new breakthrough technology that can be used to correct cancer genomes for clinical applications [214]. However, Haapaniemi et al [212] and Ihry et al [213] demonstrated that CRISPR/Cas9 genome editing technology induces p53-mediated DNA damage and that, in human PSCs, p53 inhibits CRISPR/Cas9-induced genome editing.…”

Section: Conclusion and Future Perspectivesmentioning

confidence: 99%

Potential application of cell reprogramming techniques for cancer research

Saito

Lin

Nakamura

et al. 2018

Cell. Mol. Life Sci.

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The ability to control the transition from an undifferentiated stem cell to a specific cell fate is one of the key techniques that are required for the application of interventional technologies to regenerative medicine and the treatment of tumors and metastases and of neurodegenerative diseases. Reprogramming technologies, which include somatic cell nuclear transfer, induced pluripotent stem cells, and the direct reprogramming of specific cell lineages, have the potential to alter cell plasticity in translational medicine for cancer treatment. The characterization of cancer stem cells (CSCs), the identification of oncogene and tumor suppressor genes for CSCs, and the epigenetic study of CSCs and their microenvironments are important topics. This review summarizes the application of cell reprogramming technologies to cancer modeling and treatment and discusses possible obstacles, such as genetic and epigenetic alterations in cancer cells, as well as the strategies that can be used to overcome these obstacles to cancer research.

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Tumor Organoids as a Pre-clinical Cancer Model for Drug Discovery

Cited by 419 publications

References 62 publications

Long‐term expanding human airway organoids for disease modeling

Long‐term expanding human airway organoids for disease modeling

3D tumor spheroids as in vitro models to mimic in vivo human solid tumors resistance to therapeutic drugs

Potential application of cell reprogramming techniques for cancer research

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