The Role of Cancer Stem Cells in Colorectal Cancer: From the Basics to Novel Clinical Trials

SIMPLE SUMMARY: Cancer stem cells (CSCs) fuel tumor growth, metastasis and resistance to therapy in colorectal cancer (CRC). These cells therefore represent a promising target for the treatment of CRC but are difficult to study because of the complexity of their isolation. This review presents the methods currently used to isolate colorectal CSCs as well as the techniques for characterizing these cells with their advantages and limitations. The aim of this review is to provide a state-of-the-art on the clinical relevance of CSCs in CRC by outlining current treatments for CRC, the resistance mechanisms developed by CSCs to overcome them, and ongoing clinical trials of drugs targeting CSCs in CRC. Overall, this review addresses the complexity of studying CSCs in CRC research and developing clinically effective treatments to enable CRC patients to achieve a short and long-term therapeutic response. ABSTRACT: The treatment options available for colorectal cancer (CRC) have increased over the years and have significantly improved the overall survival of CRC patients. However, the response rate for CRC patients with metastatic disease remains low and decreases with subsequent lines of therapy. The clinical management of patients with metastatic CRC (mCRC) presents a unique challenge in balancing the benefits and harms while considering disease progression, treatment-related toxicities, drug resistance and the patient’s overall quality of life. Despite the initial success of therapy, the development of drug resistance can lead to therapy failure and relapse in cancer patients, which can be attributed to the cancer stem cells (CSCs). Thus, colorectal CSCs (CCSCs) contribute to therapy resistance but also to tumor initiation and metastasis development, making them attractive potential targets for the treatment of CRC. This review presents the available CCSC isolation methods, the clinical relevance of these CCSCs, the mechanisms of drug resistance associated with CCSCs and the ongoing clinical trials targeting these CCSCs. Novel therapeutic strategies are needed to effectively eradicate both tumor growth and metastasis, while taking into account the tumor microenvironment (TME) which plays a key role in tumor cell plasticity.