Abstract
Simple SummaryColorectal cancer is one of the most frequent and lethal types of cancer. Despite advances in recent decades, our knowledge of this disease is still limited, and novel and better therapies are needed. Organoids were recently developed as a new system to culture normal and tumor cells obtained from patients subjected to surgery or endoscopic tests. Organoids are being used to dissect the molecular and genetic bases of colorectal cancer initiation and progression. In this review, we describe how patient-derived organoids can be generated, and their use to investigate in depth the tumorigenic process. We show how this system has allowed the study of colorectal tumorigenesis features for the first time, including immunotherapy, interplay with microorganisms and, more importantly, assays of drug treatments at an individualized level. Additionally, we summarize the most recent developments of what is known as organoid technology directed towards personalized medicine.Organoids were first established as a three-dimensional cell culture system from mouse small intestine. Subsequent development has made organoids a key system to study many human physiological and pathological processes that affect a variety of tissues and organs. In particular, organoids are becoming very useful tools to dissect colorectal cancer (CRC) by allowing the circumvention of classical problems and limitations, such as the impossibility of long-term culture of normal intestinal epithelial cells and the lack of good animal models for CRC. In this review, we describe the features and current knowledge of intestinal organoids and how they are largely contributing to our better understanding of intestinal cell biology and CRC genetics. Moreover, recent data show that organoids are appropriate systems for antitumoral drug testing and for the personalized treatment of CRC patients.
Highlights
We will focus on the impact that organoids are having on our knowledge and perspectives we will focus on the impact that organoids are having on our knowledge and perspectives of colorectal cancer (CRC), one of the main neoplasias in terms of incidence and mortality worldwide
Culture medium for mouse normal colon organoids requires a basis of Advanced DMEM/F12/Glutamax/HEPES medium supplied with WNT signaling activators: Rspondin and conditioned medium from Wnt3A-expressing cells
This study describes the generation of small intestine organoids from epithelial-specific porcupine-deficient mice
Summary
Organoid technology is revolutionizing research in biology and biomedicine with an increasing clinical impact on personalized medicine. CRC is a heterogenous group of neoplastic diseases that result from the malignant transformation of the epithelium lining the external surface of the large intestine This transformation or change in cell phenotype occurs as a consequence of genetic alterations (mutations) and epigenetic modifications which are thought to progressively accumulate over 10–20 years [7,8], abrupt episodes of synchronous multiple mutagenesis (chromothripsis, chromoplexy, polyploidization, kataegis) can take place [9]. This remained elusive for a long time in the case of CRC (and many other neoplasias) Another major unresolved point that has long hindered advances in the understanding and therapy of CRC has been the lack of ability to culture normal intestinal epithelial cells isolated from biopsies. These shortcomings have been solved successfully by organoid technology
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