Advances in the use of 3D colorectal cancer models for novel drug discovery.

INTRODUCTION: Colorectal cancer (CRC) is one of the most common and deadly tumors worldwide. CRC in vitro and in vivo models that recapitulate key features of human disease are essential to the development of novel and effective therapeutics. However, two-dimensional (2D) in vitro culture systems are considered too simple and do not represent the complex nature of the human tumor. However, three-dimensional (3D) models have emerged in recent years as more advanced and complex cell culture systems, able to closely resemble key features of human cancer tissues. AREAS COVERED: The authors' review the currently established in vitro cell culture models and describe the advances in the development of 3D scaffold-free models to study CRC. The authors also discuss intestinal spheroids and organoids. As well as in vitro models for drug screening and metastatic CRC (mCRC). EXPERT OPINION: The ideal CRC in vitro model is not yet established. Spheroid-based 3D models represent one of the most used approaches to recapitulate the tumor environment, overcoming some limitations of 2D models. Mouse and patient-derived organoids are more advanced models that can mimic more closely the characteristics and properties of CRC, with the possibility of including cells derived from patients with metastatic CRC.