3D Cancer Models: Depicting Cellular Crosstalk within the Tumour Microenvironment

SIMPLE SUMMARY: The tumour microenvironment is composed of multiple non-cancerous cells that communicate with the tumour cells, influencing their behaviour and impacting the progression of the disease and the response to therapy. To better understand the disease and try to predict the response of patients to therapy, there has been an effort to develop experimental strategies that could represent this complex human tumour microenvironment in a dish (in vitro). In this review, we describe the importance of each cell type and review the in vitro approaches recently developed for cultivating together the different cell types (co-culture) in a three-dimensional configuration to better represent the architecture of the tumour and cell interactions (3D models). We describe and compare the different studies and outline perspectives on the 3D modelling strategies and their potential impact in cancer research and anticancer drug discovery. ABSTRACT: The tumour microenvironment plays a critical role in tumour progression and drug resistance processes. Non-malignant cell players, such as fibroblasts, endothelial cells, immune cells and others, interact with each other and with the tumour cells, shaping the disease. Though the role of each cell type and cell communication mechanisms have been progressively studied, the complexity of this cellular network and its role in disease mechanism and therapeutic response are still being unveiled. Animal models have been mainly used, as they can represent systemic interactions and conditions, though they face recognized limitations in translational potential due to interspecies differences. In vitro 3D cancer models can surpass these limitations, by incorporating human cells, including patient-derived ones, and allowing a range of experimental designs with precise control of each tumour microenvironment element. We summarize the role of each tumour microenvironment component and review studies proposing 3D co-culture strategies of tumour cells and non-malignant cell components. Moreover, we discuss the potential of these modelling approaches to uncover potential therapeutic targets in the tumour microenvironment and assess therapeutic efficacy, current bottlenecks and perspectives.