A 3D View of Colorectal Cancer Models in Predicting Therapeutic Responses and Resistance

SIMPLE SUMMARY: Colorectal cancer is one of the most common solid tumors in the developed world. Although there have being many advances in treatment options in recent years, many patients develop resistance to treatment which impacts their outcome. It has been shown that cancer cells can interact with cells around them in the colon to help the tumor to progress, expand, and resist death in response to treatment. To study how the cancer cells interact with the different cells in the colon, 3D models can be used. They allow many different cell types to be incorporated together and investigation of their response to drugs over time. This review aims to summarize the advantages and disadvantages of 3D models currently being used to study colorectal cancer, as well as suggesting how these models could be useful in studying drug resistance and the development of new drugs. ABSTRACT: Although there have been many advances in recent years for the treatment of colorectal cancer (CRC), it still remains the third most common cause of cancer-related deaths worldwide. Many patients with late stage CRC display resistance to multiple different therapeutics. An important aspect in developing effective therapeutics for CRC patients is understanding the interactions that take place in the tumor microenvironment (TME), as it has been shown to contribute to drug resistance in vivo. Much research over the past 100 years has focused on 2D monolayer cultures or in vivo studies, however, the efficacy in translating these to the clinic is very low. More recent studies are turning towards developing an effective 3D model of CRC that is clinically relevant, that can recapitulate the TME in vitro and bridge the gap between 2D cultures and in vivo studies, with the aim of reducing the use of animal models in the future. This review summarises the advantages and limitations of different 3D CRC models. It emphasizes how different 3D models may be optimised to study cellular and extracellular interactions that take place in the TME of CRC in an effort to allow the development of more translatable effective treatment options for patients.