Impact of Intracellular Signaling in Colorectal Cancer (CRC)

Abstract

Colorectal cancer (CRC) is one of the leading causes of cancer death worldwide. The development of local and/or distant tumor recurrences after completed anti-cancer therapy is a major problem in the treatment of CRC. The problem of CRC recurrences should be discovered in details in order to propose predictive biomarkers and improve therapy results in CRC patients. A growing body of evidence supports an idea that development of CRC recurrences may be closely associated with therapy-resistant carcinoma stem cells. According to the hypothesis of carcinoma stem cells (also referred to as tumor-initiating cells), malignant tumors contain a fraction of cells possessing the abilities for self-renewal and generation of heterogeneous lineages of cancer cells comprising the tumor [1,2]. Therefore, it is logical to suggest that the malignant tumor could be cured only when all cancer stem cells will be killed. In order to improve treatment outcome in patients with recurrent and/or metastatic CRC (mCRC), the reliable biomarkers and targets to detect and destroy CRC stem cells are urgently needed. Nowadays, various targeting therapeutics are used in combination with conventional therapy approaches. It is generally believed that targeted compounds could effectively kill tumor cells, because they are directed against products of genes possessing causative link with tumorigenesis. However, the existing targeted therapeutics reveal very limited clinical benefit in mCRC patients [3]. It is possible to suggest that the low response rate and disappointed clinical benefit might be related to the ineffective killing of CRC stem cells, whereas the majority population of non-stem cells are effectively destroyed upon treatment using targeted compounds.