Stem cells in colon cancer

Abstract

Colorectal cancer (CRC) is still one of the most commonly diagnosed and lethal cancers worldwide. The classic model of CRC carcinogenesis involves a multistep process of oncogenes activation and inactivation of tumor suppressor genes. But the cell of origin and the type of cells that propagate the tumor after its initiation are still unknown. The concept of Cancer Stem Cells (CSC) was first developed for hematologic malignancies and later applied to solid neoplasias. This model suggests that tumors are hierarchically organized and only CSCs possess the ability to initiate tumors and due to their resistance to conventional treatments, they are also responsible for tumor relapse. The problem lies still in their identification which remains controversial due to the lack of specific molecular markers. Colon CSCs were originally identified through the expression of the CD133. However, it is not definitively proven that CD133 is a reliable marker of colon CSCs and other cell surface markers, such as CD44, CD166, Musashi-1, CD24 among others have also been suggested. Moreover, there are several molecular pathways (Wnt or Notch) as well as the complex crosstalk network between microenvironment and CSCs which are relevant for CRC. Therefore the design of CSC-targeted agents would enhance responsiveness to traditional treatments and eventually reduce local recurrence and metastasis. This review will discuss the newly introduced CSC model in CRC, the identification markers and the pathways involved in the design of novel therapeutic approaches and also the limitations associated with this model.