Hervieu Céline, Christou Niki, Battu Serge, Mathonnet Muriel
EA 3842 CAPTuR "Control of Cell Activation in Tumor Progression and Therapeutic Resistance", Faculty of Medicine, Genomics, Environment, Immunity, Health and Therapeutics (GEIST) Institute, University of Limoges, 87025 Limoges CEDEX, France.
Department of General, Endocrine and Digestive Surgery, University Hospital of Limoges, 87025 Limoges CEDEX, France.
Cancers (Basel). 2021 Mar 4;13(5):1092. doi: 10.3390/cancers13051092.
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.
多年来，可用于治疗结直肠癌（CRC）的方案有所增加，显著提高了CRC患者的总生存率。然而，转移性疾病的CRC患者的缓解率仍然很低，并且随着后续治疗线数的增加而降低。转移性CRC（mCRC）患者的临床管理在平衡获益与风险方面面临独特挑战，同时要考虑疾病进展、治疗相关毒性、耐药性以及患者的整体生活质量。尽管治疗初期取得了成功，但耐药性的出现可导致癌症患者治疗失败和复发，这可能归因于癌症干细胞（CSC）。因此，结直肠癌干细胞（CCSC）不仅导致治疗耐药性，还与肿瘤起始和转移发展有关，使其成为CRC治疗有吸引力的潜在靶点。本综述介绍了现有的CCSC分离方法、这些CCSC的临床相关性、与CCSC相关的耐药机制以及针对这些CCSC的正在进行的临床试验。需要新的治疗策略来有效根除肿瘤生长和转移，同时考虑到在肿瘤细胞可塑性中起关键作用的肿瘤微环境（TME）。
