Organoids reveal cancer dynamics

Kuo, Calvin J.; Curtis, Christina

doi:10.1038/d41586-018-03841-x

Cited by 16 publications

(11 citation statements)

References 13 publications

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“…Organoids, which are becoming increasingly popular in basic and translational cancer research, require a scaffold mimicking the ECM to enable the three-dimensional growth of patient-derived tumor cells and allow for an extensive genetic characterization of tumor cells gained from patient probes [225,226]. They are highly useful for drug pre-screening [227] and thus for a potential selection of a beneficial combination treatment for certain tumor types.…”

Section: Summarizing Discussionmentioning

confidence: 99%

Tumor targeting via EPR: Strategies to enhance patient responses

Golombek

May

Theek

et al. 2018

Advanced Drug Delivery Reviews

967

699

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The tumor accumulation of nanomedicines relies on the enhanced permeability and retention (EPR) effect. In the last 5-10 years, it has been increasingly recognized that there is a large inter- and intra-individual heterogeneity in EPR-mediated tumor targeting, explaining the heterogeneous outcomes of clinical trials in which nanomedicine formulations have been evaluated. To address this heterogeneity, as in other areas of oncology drug development, we have to move away from a one-size-fits-all tumor targeting approach, towards methods that can be employed to individualize and improve nanomedicine treatments. To this end, efforts have to be invested in better understanding the nature, the complexity and the heterogeneity of the EPR effect, and in establishing systems and strategies to enhance, combine, bypass and image EPR-based tumor targeting. In the present manuscript, we summarize key studies in which these strategies are explored, and we discuss how these approaches can be employed to enhance patient responses.

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Section: Summarizing Discussionmentioning

confidence: 99%

Tumor targeting via EPR: Strategies to enhance patient responses

Golombek

May

Theek

et al. 2018

Advanced Drug Delivery Reviews

967

699

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“…Organoids have tremendous promise for modelling human cancers and exhibit their utility for translational and clinical cancer research [ 77 , 78 ]. Up to now, organoids have been successfully developed from multiple cancer types, including gastric cancer [ 19 , 20 ], intestinal cancer [ 19 ], liver cancer [ 21 ], pancreatic cancer [ 79 – 81 ], prostate cancer [ 82 – 84 ], bladder cancer [ 23 ] and breast cancer [ 22 , 85 ].…”

Section: Application Of Organoid Technologymentioning

confidence: 99%

Organoid technology in disease modelling, drug development, personalized treatment and regeneration medicine

et al. 2018

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Organoid technology bridges the gap between conventional two-dimensional cell line culture and in vivo models. The near-physiological technology can virtually recapitulates organ development and human diseases, such as infectious diseases, genetic abnormality and even cancers. In addition, organoids can more accurately predict drug responses, and serve as an excellent platform for drug development, including efficacy evaluation, toxicity testing and pharmacokinetics analysis. Furthermore, organoids can also be exploited to explore the possible optimized treatment strategies for each individual patient. Besides, organoid technology is a promising strategy for regeneration medicine and transplantation use, which can overcome the deficiency in the supply of healthy donor tissues and inherent immunological rejection through establishing isogenic organoids from minuscule amounts of patient biopsies. Collectively, organoids hold enormous potential for clinical applications and bring basic research closer to clinical practice. In this review, we described common organoid lines, summarized the potential clinical applications, and outlined the current limitations.

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“…Observations from these studies suggest that intermittent and adaptive therapy and chronic control of tumors hold promise for combating resistance and should be tested more often in clinical trials in the future. These trials should be guided by future research that capitalizes on emerging preclinical models such as patient-derived organoids (PDOs) and patient-derived xenografts (PDXs), which can offer more clinically-relevant systems to facilitate high fidelity clinical translation [137][138][139].…”

Section: Discussionmentioning

confidence: 99%

Polytherapy and Targeted Cancer Drug Resistance

2019

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A current challenge in cancer treatment is drug resistance. Even the most effective therapies often fail to produce complete and durable tumor response and ultimately give rise to therapy resistance and tumor relapse. How resistance arises in cancer remains incompletely understood. While drug resistance in cancer is thought to be driven by irreversible genetic mutations, emerging evidence also implicates reversible proteomic and epigenetic mechanisms in the development of drug resistance. Tumor microenvironment-mediated mechanisms and tumor heterogeneity can significantly contribute to cancer treatment resistance. Here, we discuss the diverse and dynamic strategies that cancers use to evade drug response, the promise of upfront combination and intermittent therapies and therapy switching in forestalling resistance, and epigenetic reprogramming to combat resistance.

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Organoids reveal cancer dynamics

Cited by 16 publications

References 13 publications

Tumor targeting via EPR: Strategies to enhance patient responses

Tumor targeting via EPR: Strategies to enhance patient responses

Organoid technology in disease modelling, drug development, personalized treatment and regeneration medicine

Polytherapy and Targeted Cancer Drug Resistance

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