Organoid Models for Cancer Research-From Bed to Bench Side and Back.

Carolin Kastner,Hanna Deinlein,Stefanie Schmidt,Anne Hendricks,Mohammed Hankir,Armin Wiegering,Christoph-Thomas Germer

doi:10.3390/cancers13194812

Carolin Kastner, Hanna Deinlein + Show 5 more

Open Access

https://doi.org/10.3390/cancers13194812

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Abstract

Simple SummaryDespite significant strides in multimodal therapy, cancers still rank within the first three causes of death especially in industrial nations. A lack of individualized approaches and accurate preclinical models are amongst the major barriers that limit the development of novel therapeutic options and drugs. Recently, the 3D culture system of organoids was developed which stably retains the genetic and phenotypic characteristics of the original tissue, healthy as well as diseased. In this review, we summarize current data and evidence on the relevance and reliability of such organoid culture systems in cancer research, focusing on their role in drug investigations (in a personalized manner).Organoids are a new 3D ex vivo culture system that have been applied in various fields of biomedical research. First isolated from the murine small intestine, they have since been established from a wide range of organs and tissues, both in healthy and diseased states. Organoids genetically, functionally and phenotypically retain the characteristics of their tissue of origin even after multiple passages, making them a valuable tool in studying various physiologic and pathophysiologic processes. The finding that organoids can also be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research. In this review, we discuss the potential of organoids to close the gap between preclinical in vitro and in vivo models as well as clinical trials in cancer research focusing on drug investigation and development.

Highlights

Despite major advances in all aspects of multimodal therapy, cancer remains one of the leading causes of death worldwide, accounting for almost 10 million deaths in 2020 [1,2]
The finding that organoids can be established from tumor tissue or can be engineered to recapitulate tumor tissue has dramatically increased their use in cancer research
The organoid culture system can be valuable for assessing the therapeutic response of recurrent tumors and potential resistances developing from primary to recurrent tumors. This has been shown by comparing drug responses in matched organoid lines of a high-grade serous (HGS) ovarian cancer patient derived from a primary chemosensitive and recurrent chemoresistant tumor

Summary

Introduction

Despite major advances in all aspects of multimodal therapy, cancer remains one of the leading causes of death worldwide, accounting for almost 10 million deaths in 2020 [1,2]. There are several other limitations when trying to extrapolate results from model systems such as 2D cell cultures to the human in vivo situation [8] This might explain why only 3.4% of cancer-targeting drugs are approved for clinical use after passing the clinical trial process [9,10,11]. We know that starting from a (tissue-specific) stem/progenitor cell, organoids are self-organizing organotypic structures that at least partially show cellular heterogeneity, basic functional and structural aspects of the tissue of origin [14]. Based on their properties, organoids are thought to fill the gap between “classic” cell lines and in vivo models

Origin and Establishment of Organoid Models

Findings

Conclusions and Perspectives