Preclinical models as patients' avatars for precision medicine in colorectal cancer: past and future challenges

Colorectal cancer (CRC) is a complex and heterogeneous disease, characterized by dismal prognosis and low survival rate in the advanced (metastatic) stage. During the last decade, the establishment of novel preclinical models, leading to the generation of translational discovery and validation platforms, has opened up a new scenario for the clinical practice of CRC patients. To bridge the results developed at the bench with the medical decision process, the ideal model should be easily scalable, reliable to predict treatment responses, and flexibly adapted for various applications in the research. As such, the improved benefit of novel therapies being tested initially on valuable and reproducible preclinical models would lie in personalized treatment recommendations based on the biology and genomics of the patient's tumor with the overall aim to avoid overtreatment and unnecessary toxicity. In this review, we summarize different in vitro and in vivo models, which proved efficacy in detection of novel CRC culprits and shed light into the biology and therapy of this complex disease. Even though cell lines and patient-derived xenografts remain the mainstay of colorectal cancer research, the field has been confidently shifting to the use of organoids as the most relevant preclinical model. Prioritization of organoids is supported by increasing body of evidence that these represent excellent tools worth further therapeutic explorations. In addition, novel preclinical models such as zebrafish avatars are emerging as useful tools for pharmacological interrogation. Finally, all available models represent complementary tools that can be utilized for precision medicine applications.