No abstract

Gene signatures derived from cancer stem cells (CSCs) predict tumor recurrence for many forms of cancer. Here, we derived a gene signature for colorectal CSCs defined by high Wnt signaling activity, which in agreement with previous observations predicts poor prognosis. Surprisingly, however, we found that elevated expression of Wnt targets was actually associated with good prognosis, while patient tumors with low expression of Wnt target genes segregated with immature stem cell signatures. We discovered that several Wnt target genes, including ASCL2 and LGR5, become silenced by CpG island methylation during progression of tumorigenesis, and that their re-expression was associated with reduced tumor growth. Taken together, our data show that promoter methylation of Wnt target genes is a strong predictor for recurrence of colorectal cancer, and suggest that CSC gene signatures, rather than reflecting CSC numbers, may reflect differentiation status of the malignant tissue.

Resistance to tumor therapy is an unsolved problem in cancer treatment. A plethora of studies have attempted to explain this phenomenon and many mechanisms of resistance have been suggested over recent decades. The concept of cancer stem cells (CSCs), which describes tumors as hierarchically organized, has added a new level of complexity to therapy failure. CSCs are the root of cancers and resist chemo‐ and radiotherapy, explaining cancer recurrence even many years after therapy is ended. This review discusses briefly CSCs in cancers, gives an overview of the role of CSCs in therapy resistance, and discusses the potential means of targeting these therapy‐resistant tumor cells.