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Organoids in cancer research.
Literature Information
| DOI | 10.1038/s41568-018-0007-6 |
|---|---|
| PMID | 29692415 |
| Journal | Nature reviews. Cancer |
| Impact Factor | 66.8 |
| JCR Quartile | Q1 |
| Publication Year | 2018 |
| Times Cited | 864 |
| Keywords | Organoids, Cancer Research, Disease Modeling, Patient-Specific Drug Testing |
| Literature Type | Journal Article, Research Support, Non-U.S. Gov't, Review |
| ISSN | 1474-175X |
| Pages | 407-418 |
| Issue | 18(7) |
| Authors | Jarno Drost, Hans Clevers |
TL;DR
Recent advancements in in vitro 3D culture technologies, particularly organoids, provide innovative and more physiological models for human cancer research, facilitating the translation of basic research into effective treatments. This review evaluates tumor organoid protocols and their potential for disease modeling, patient-specific drug testing, and the development of individualized treatment regimens.
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Organoids · Cancer Research · Disease Modeling · Patient-Specific Drug Testing
Abstract
The recent advances in in vitro 3D culture technologies, such as organoids, have opened new avenues for the development of novel, more physiological human cancer models. Such preclinical models are essential for more efficient translation of basic cancer research into novel treatment regimens for patients with cancer. Wild-type organoids can be grown from embryonic and adult stem cells and display self-organizing capacities, phenocopying essential aspects of the organs they are derived from. Genetic modification of organoids allows disease modelling in a setting that approaches the physiological environment. Additionally, organoids can be grown with high efficiency from patient-derived healthy and tumour tissues, potentially enabling patient-specific drug testing and the development of individualized treatment regimens. In this Review, we evaluate tumour organoid protocols and how they can be utilized as an alternative model for cancer research.
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Primary Questions Addressed
- How do organoids compare to traditional 2D cell cultures in terms of mimicking the tumor microenvironment?
- What specific advancements in organoid technology have significantly improved their application in cancer research?
- In what ways can patient-derived organoids facilitate personalized medicine in oncology?
- What are the limitations of using organoids for cancer research, and how can these be addressed in future studies?
- How do genetic modifications in organoids enhance their utility for modeling specific cancer types and treatment responses?
Key Findings
1. Research Background and Purpose: The study focuses on the recent advancements in 3D culture technologies, particularly organoids, which are emerging as pivotal tools in cancer research. Traditional cancer models often fail to accurately mimic the complex interactions and microenvironments of human tumors. The purpose of this review is to evaluate the development and application of organoids as a more physiological model for cancer research, thereby bridging the gap between basic research and clinical application, ultimately leading to more effective cancer treatments.
2. Main Methods and Findings: The review discusses the methodologies for generating wild-type organoids from both embryonic and adult stem cells. These organoids exhibit self-organizing capabilities that replicate critical characteristics of their tissue of origin. The authors highlight the ability to genetically modify organoids, which facilitates the modeling of various cancers in an environment that closely resembles human physiology. Additionally, the review underscores the efficiency of deriving organoids from patient tissues, both healthy and tumor samples, which paves the way for personalized drug testing. The findings indicate that organoids can serve as a promising platform for assessing the efficacy of potential cancer therapies tailored to individual patient profiles.
3. Core Conclusions: Organoids represent a significant leap forward in cancer modeling, providing a more accurate and representative system for studying tumor biology and treatment responses. They retain many features of the original tissues, including genetic and phenotypic characteristics, and can be manipulated to model various stages of cancer. This makes them invaluable for investigating cancer mechanisms and for evaluating treatment options in a patient-specific manner.
4. Research Significance and Impact: The implications of this research are profound, as organoids could transform the landscape of cancer research and treatment. Their ability to mimic the human tumor environment allows for more effective preclinical testing of new therapies, potentially accelerating the translation of research findings into clinical practice. Moreover, the capacity for personalized medicine through patient-derived organoids could lead to individualized treatment regimens, improving patient outcomes and minimizing the side effects associated with less targeted therapies. By fostering a better understanding of tumor biology and therapy responses, organoids hold the promise of enhancing the efficacy of cancer treatments and ultimately improving survival rates for cancer patients.
Literatures Citing This Work
- Organoid Models of Human Liver Cancers Derived from Tumor Needle Biopsies. - Sandro Nuciforo;Isabel Fofana;Matthias S Matter;Tanja Blumer;Diego Calabrese;Tujana Boldanova;Salvatore Piscuoglio;Stefan Wieland;Femke Ringnalda;Gerald Schwank;Luigi M Terracciano;Charlotte K Y Ng;Markus H Heim - Cell reports (2018)
- Microenvironmental regulation of cancer cell metabolism: implications for experimental design and translational studies. - Alexander Muir;Laura V Danai;Matthew G Vander Heiden - Disease models & mechanisms (2018)
- Personalized Cancer Models for Target Discovery and Precision Medicine. - Carla Grandori;Christopher J Kemp - Trends in cancer (2018)
- Applications of tumor chip technology. - Stephanie J Hachey;Christopher C W Hughes - Lab on a chip (2018)
- Inhibition of cIAP1 as a strategy for targeting c-MYC-driven oncogenic activity. - Haoyan Li;Yanjia Fang;Chunyi Niu;Hengyi Cao;Ting Mi;Hong Zhu;Junying Yuan;Jidong Zhu - Proceedings of the National Academy of Sciences of the United States of America (2018)
- 3D microfluidic ex vivo culture of organotypic tumor spheroids to model immune checkpoint blockade. - Amir R Aref;Marco Campisi;Elena Ivanova;Andrew Portell;Dalia Larios;Brandon P Piel;Natasha Mathur;Chensheng Zhou;Raven Vlahos Coakley;Alan Bartels;Michaela Bowden;Zach Herbert;Sarah Hill;Sean Gilhooley;Jacob Carter;Israel Cañadas;Tran C Thai;Shunsuke Kitajima;Valeria Chiono;Cloud P Paweletz;David A Barbie;Roger D Kamm;Russell W Jenkins - Lab on a chip (2018)
- Recent advances in combinatorial drug screening and synergy scoring. - Tea Pemovska;Johannes W Bigenzahn;Giulio Superti-Furga - Current opinion in pharmacology (2018)
- Prediction of DNA Repair Inhibitor Response in Short-Term Patient-Derived Ovarian Cancer Organoids. - Sarah J Hill;Brennan Decker;Emma A Roberts;Neil S Horowitz;Michael G Muto;Michael J Worley;Colleen M Feltmate;Marisa R Nucci;Elizabeth M Swisher;Huy Nguyen;Chunyu Yang;Ryuji Morizane;Bose S Kochupurakkal;Khanh T Do;Panagiotis A Konstantinopoulos;Joyce F Liu;Joseph V Bonventre;Ursula A Matulonis;Geoffrey I Shapiro;Ross S Berkowitz;Christopher P Crum;Alan D D'Andrea - Cancer discovery (2018)
- Organoid technology and applications in cancer research. - Hanxiao Xu;Xiaodong Lyu;Ming Yi;Weiheng Zhao;Yongping Song;Kongming Wu - Journal of hematology & oncology (2018)
- Native-mimicking in vitro microenvironment: an elusive and seductive future for tumor modeling and tissue engineering. - Girdhari Rijal;Weimin Li - Journal of biological engineering (2018)
... (854 more literatures)
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