Metastatic Cancer Stem Cells: New Molecular Targets for Cancer Therapy

G.      J. Leiros; M.      E. Balana

doi:10.2174/138920111798377094

Abstract

The cancer stem cell (CSC) hypothesis, predicts that a small subpopulation of cancer cells that possess “stemlike” characteristics, are responsible for initiating and maintaining cancer growth. According to the CSC model the many cell populations found in a tumour might represent diverse stages of differentiation. From the cellular point of view metastasis is considered a highly inefficient process and only a subset of tumour cells is capable of successfully traversing the entire metastatic cascade and eventually re-initiates tumour growth at distant sites. Some similar features of both normal and malignant stem cells suggest that CSCs are not only responsible for tumorigenesis, but also for metastases. The CSC theory proposes that the ability of a tumour to metastasize is an inherent property of a subset of CSCs. The similar biological characteristics shared by normal stem cells (NSCs) and CSCs mainly implicate self-renewal and differentiation potential, survival ability, niche-specific microenvironment requirements and specific homing to metastatic sites and may have important implications in terms of new approaches to cancer therapy in the metastatic setting. There are several agents targeting many of these CSC features that have shown to be effective both in vitro and in vivo. Although clinical trials results are still preliminary and continue under investigation, these new therapies are very promising. The identification of new therapeutic targets and drugs based on CSC model constitutes a great challenge.

Keywords: Aberrant differentiation, cancer stem cells, metastasis molecular targets, metastatic process, mobilisation and metastasis, self-renewal ability, stem cell markers, normal stem cells (NSCs), radio-chemotherapy, human leukaemia, polycythemia vera, colorectal cancer, matrix metalloproteinases (MMP9), acute myeloid leukaemia (AML)