Abstract
Currently, colorectal cancer is still the third leading cause of cancer-related mortality, and the incidence is rising. It is a long time since the researchers used cancer cell lines and animals as the study subject. However, these models possess various limitations to reflect the cancer progression in the human body. Organoids have more clinical significance than cell lines, and they also bridge the gap between animal models and humans. Patient-derived organoids are three-dimensional cultures that simulate the tumor characteristics in vivo and recapitulate tumor cell heterogeneity. Therefore, the emergence of colorectal cancer organoids provides an unprecedented opportunity for colorectal cancer research. It retains the molecular and cellular composition of the original tumor and has a high degree of homology and complexity with patient tissues. Patient-derived colorectal cancer organoids, as personalized tumor organoids, can more accurately simulate colorectal cancer patients’ occurrence, development, metastasis, and predict drug response in colorectal cancer patients. Colorectal cancer organoids show great potential for application, especially preclinical drug screening and prediction of patient response to selected treatment options. Here, we reviewed the application of colorectal cancer organoids in disease model construction, basic biological research, organoid biobank construction, drug screening and personalized medicine, drug development, drug toxicity and safety, and regenerative medicine. In addition, we also displayed the current limitations and challenges of organoids and discussed the future development direction of organoids in combination with other technologies. Finally, we summarized and analyzed the current clinical trial research of organoids, especially the clinical trials of colorectal cancer organoids. We hoped to lay a solid foundation for organoids used in colorectal cancer research.
Highlights
Colorectal cancer (CRC) ranked the third one in tumor incidence of all malignant tumors and the second one in cancer-related mortality worldwide (Keum and Giovannucci, 2019)
PDOs test predicted the response to biopsy lesions in more than 80% of patients treated with irinotecan in metastatic CRC patients, without misclassifying patients who would have benefited from this treatment
Human CRC organoids further our fundamental understanding of CRC occurrence and development, biology, and disease, promising tools for a wide range of biomedical applications, from disease modeling to drug screen and personalized medicine
Summary
Colorectal cancer (CRC) ranked the third one in tumor incidence of all malignant tumors and the second one in cancer-related mortality worldwide (Keum and Giovannucci, 2019). The clinical data showed the cure rate approaching 90% after surgery when CRC is diagnosed in the early stage It was only 10% of the 5-years survival rate of patients with metastatic CRC that cancer cells spread to distant lymph nodes or other organs (Relier et al, 2016). A kind of in vitro culture system, contains self-renewing stem cells that differentiate into various organ-specific cell types and tissues, a threedimensional (3D) structure that assumes a similar organization and functionality as an organ. It overcomes many limitations of traditional models. A variety of cancer organoids have been successfully established, which includes breast cancer
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