Cancer stem cells (CSCs) are the main culprits involved in therapy resistance and disease recurrence in colorectal carcinoma (CRC). Results using cell culture, animal models and tissues from patients with CRC suggest the indispensable roles of colorectal CSCs in therapeutic failure. Conventional therapies target proliferating and mature cancer cells, while CSCs are mostly quiescent and poorly differentiated, thereby they can easily survive chemotherapeutic insults. The aberrant activation of Wnt/β-catenin, Notch, Hedgehog, Hippo/YAP (Yes-associated protein) and phosphatidylinositol 3-kinase/protein kinase B facilitates CSCs with excessive self-renewal and therapy resistance property in CRC. CSCs survive the chemo-radiotherapies by escaping therapy mediated DNA damage via altering the cell cycle checkpoints, increasing DNA damage repair capacity and by an efficient scavenging of reactive oxygen species. Furthermore, dysregulations of miRNAs e.g., miR-21, miR-93, miR-203, miR-215, miR-497 etc., modulate the therapeutic sensitivity of colorectal CSCs by regulating growth and survival signalling. In addition, a reversible quiescent G₀ state and the re-entering cell cycle capacity of colorectal CSCs can accelerate tumour regeneration after treatment. Moreover, switching to favourable metabolic signatures during a therapeutic regimen will add more complexity in therapeutic outcomes against CSCs. Therapeutic strategies targeting these underlying mechanisms of CSCs’ therapy resistance could provide a promising outcome, however, deep understanding and concerted research are necessary to design novel therapies targeting CSCs. To conclude, the understanding of these mechanisms of CSC in CRC could lead to the improved management of patients with CRC.

Cancer stem cells (CSCs) are cancer cells that are responsible for initiation, progression, metastasis, and recurrence in cancer. The aim of this review was to analyze the markers for identifying of CSCs in colorectal carcinoma, as well as the prognostic and therapeutic implications of these markers in the cancer. CSCs are insensitive to the current drug regimens. In colorectal carcinoma, markers, including Nanog, Oct-4, SOX-2, Lgr-5, CD133, CD24, CD29, ALDH1, EpCAM, CD44, CD166, and CD26, are commonly used for the identification and isolation of CSCs. In addition, ALDH1, CD24, CD44, CD133, CD166, EpCAM, Lgr-5, Nanog, and SOX-2 could have clinical roles in predicting pathological stages, cancer recurrence, therapy resistance, and patients' survival in patients with colorectal carcinoma. In light of the current knowledge of CSCs in colorectal carcinoma, novel potential therapeutic strategies, such as development of monoclonal antibodies or immunotoxins and targeting various cell surface molecules in colorectal CSCs and/or components of signaling pathways, have been developed. This could open new opportunities for the better management of patients with colorectal carcinoma.