Cancer stem cells are the origins of tumor growth and recurrences

Abstract

The hypothesis that tumorigenic stem cells arises from the mutated stem cells suggests that cancer can be viewed as an aberrant organ initiated by tumorigenic cancer cells with stem-cell qualities. The tumor initiator cell or tumor stem cell/ cancer stem cell (CSC) is possible origins ofnormal stem cell or progenitor cells. The existence of such a CSC population may represent only a small fraction of a tumor possessing the ability to regenerate tumors through aberrant proliferation and self-renewal, but most cancer cells lack this ability. A central question in stem cell and CSC biology is, which cells can be transformed to generate tumors? With the growing evidence that CSC exist in malignancies of haematopoietic origin and in most solid tumors, it is becoming increasingly important to understand the molecular mechanisms that regulate self-renewal and differentiation because mutation of genes involved in these pathways likely participates in tumor growth. Studies of normal stem cell and CSC from the same tissue have suggested that the ontogeny of tumors. That signaling pathways such as Wnt, BMP and Notch have similar effects on normal stem cell and CSC self-renewal implys that common molecular pathways regulate both populations. Stem cell biology has provided a platform to address many questions in developmental biology. Further understanding the biology of stem cell, cancer cell, and CSC will contribute to the identification of molecular targets important for future therapies. To know the biology of CSC, we first should identify the unique characteristics of stem cells. A normal adult stem cell is defined as a somatic cell undergoing extensive cell division and has the potential to give rise to both stem cells and cells that differentiate into specialized cells. A normal stem cell must possess two qualities to play its natural function: self-renewal and differentiation. Self-renewal is an important ability of stem cells, indicating a special cell division that enables a stem cell to develop another stem cell with essentially the same development and replication potential. The capability to self-renewal causes the stem cell expansion in response to local or systemic signals, which start massive proliferation and maintenance of a tissue specific undifferentiated pool of cells in the organ or tissue. Differentiation is the second function of a stem cell and involves the development of daughter cells that become tissue specific specialized cells. Studies have demonstrated that the CSCs are likely to share many of the properties of normal stem cells, and that the CSCs are source of tumor recurrences and/or metastasis after apparently complete remissions. Although there is an argument about CSC model that may overlook the complexity of the interactions which occur within a tumor and between a tumor and its environment, evidence that many cancers are driven by CSC has important clinical implications. For example, conventional therapies may shrink tumors by killing mainly cells with limited proliferative potential, however, CSCs are less sensitive to these therapies, then they will remain viable after therapy and re-establish the tumor. Therefore, CSC model has favored the conceptual development of targeted therapies towards CSC’s “stemness”. However, how to achieve CSC eradication is emergent to overcome the major barrier. Here we describe latest therapeutic approaches based on the “stemness” of CSC that may allow us to discover the effective methods for eradicating seeds of malignant tumor cells. This includes targeted therapy directed toward CSC by surface specific markers, survival niche, blocking CSC critical signal pathways, inhibiting CSC efficient DNA repair, manipulation of ncRNAs, screening drug-resistance of CSC in three dimensional culture, CSC vaccines as well as CSC nanotheranostics.