Multi-Organ-on-Chip approach to study the impact of inter-organ communication on the efficacy and side effects of cancer therapy

Abstract

Cancer is one of the pathological conditions of the human body, which, due to its tissue diversity, is not fully understood. Currently used preclinical in vitro cell or animal models do not reflect the complexity and functional features of the human body, including its pathological conditions such as cancer. This fact is related to poor predictions of the effectiveness of newly developed drugs. Therefore, in our work, we focused on creating a tool that allows the reproduction of important morphological and biochemical features of the tumor in vivo, such as three-dimensional (3D) structure, heterogeneity, the presence of extracellular matrix (ECM), and the appropriate scale (volume to surface ratio). Moreover, the presented Multi-Organ-on-Chip (MOC) tool allows us to evaluate the effects of anticancer therapy, considering hepatic metabolism (liver model) and the assessment of its side effects on a selected organ (skin model). Our research shows that incorporating multiple organ models in one in vitro tool affects the viability and metabolic activity of the cells that constitute them. Moreover, we have shown how important it is to consider hepatic metabolism when evaluating the therapeutic effectiveness of two selected chemotherapy drugs, 5-Fluorouracil (5-FU) and its prodrug Capecitabine (CAP).