Advances towards the use of gastrointestinal tumor patient-derived organoids as a therapeutic decision-making tool

Abstract

In December 2022 the US Food and Drug Administration (FDA) removed the requirement that drugs in development must undergo animal testing before clinical evaluation, a declaration that now demands the establishment and verification of ex vivo preclinical models that closely represent tumor complexity and that can predict therapeutic response. Fortunately, the emergence of patient-derived organoid (PDOs) culture has enabled the ex vivo mimicking of the pathophysiology of human tumors with the reassembly of tissue-specific features. These features include histopathological variability, molecular expression profiles, genetic and cellular heterogeneity of parental tissue, and furthermore growing evidence suggests the ability to predict patient therapeutic response. Concentrating on the highly lethal and heterogeneous gastrointestinal (GI) tumors, herein we present the state-of-the-art and the current methodology of PDOs. We highlight the potential additions, improvements and testing required to allow the ex vivo of study the tumor microenvironment, as well as offering commentary on the predictive value of clinical response to treatments such as chemotherapy and immunotherapy.

Cholinergic Mechanisms in Gastrointestinal Neoplasia

“…The use of patient-derived organoids (PDO) addresses some of the aforementioned concerns, as it allows for threedimensional representation of the GI tumor microenvironment, including tumor-stroma interactions, and includes more soluble factors present in the tumor milieu. Others have reviewed the utility of PDOs in GI cancer research in greater depth [61]. With proper passaging, organoid systems can be cultured long-term, allowing for longitudinal studies of responses to various treatments.…”