The Roles of Cancer Stem Cells and Therapy Resistance in Colorectal Carcinoma

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.…