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

Abstract

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.

Replacement, Reduction, and Refinement of Animal Experiments in Anticancer Drug Development: The Contribution of 3D In Vitro Cancer Models in the Drug Efficacy Assessment

“…Although these studies were typically designed with the primary aim of personalized medicine, they provided strong evidence of PDO translational potential. These works were already systematically reviewed in [ 188 , 189 , 190 ], resulted to be heterogeneous for a multitude of factors. They differed in (i) investigated tumor type and anticancer treatments, (ii) patient cohort size, (iii) study design, (iv) definition of treatment response in PDOs as well in patients, (v) inclusion of parallel PDXs, and (vi) strength of the applied statistical methods and correlation significance.…”

Moving toward precision medicine to predict drug sensitivity in patients with metastatic breast cancer

“… 94 Therefore, 3D cell cultures represent an ideal preclinical model not only to study cancer development, but also as personalized platforms for patient-specific drug screening. The potentiality of organoids as a drug screening platform was evaluated with encouraging results, 95 and ongoing trials are exploring the possibility of guiding treatment choice according to organoid sensitivity (NCT04931381). In addition, patient-derived xenograft, developed by transplanting tumoral cells into immunodeficient mice, represents a further tool to preclinically analyze tumor features better recapitulating cancer heterogeneity and tumor microenvironment.…”

Preclinical Evaluation of CAR T Cell Function: In Vitro and In Vivo Models

“…Organoids are three-dimensional, multi-cellular structures that resemble the spatial characteristics of the original tissue [ 73 , 74 ]. Tumor-derived organoids (TDOs) have been initially generated from normal organoids by introducing pro-tumorigenic mutations, such as the losses of APC and TP53 [ 75 , 76 ], and then directly from fresh tumor specimens, which capture the cellular and molecular diversity of the clinical samples [ 77 , 78 , 79 , 80 , 81 , 82 ].…”