Cancer stem cells, their origin and niche: A search for the therapeutic target

Cancer is a general term to define a group of genetic alterations and the subsequent phenotypic and physiological changes at the cellular level, leading to accelerated death of the host. According to The World Health Organisation (WHO), it is the second leading factor for human deaths globally. Cancer is such a difficult challenge for mankind because of its ability to relapse even after detailed treatments with chemotherapeutic agents and ionizing radiations. This can be explained by the emerging concept of 'tumor initiating cells' or 'cancer stem cells' (CSCs) which comprise a pluripotent and genomically dynamic subpopulation of the tumor microenvironment, occupying only 0.1%-3% of the total tumor population. Despite their emerging significance in disease progression and recurrence, the origin of these CSCs and their complex interaction with the corresponding CSC niche still remain to be elusive. In this review, we make an attempt to unwind the mystery of the origin of the CSCs as well as focus on the well-established cross-talk mechanisms between the CSCs and their niche components. Lastly, we try to find alternative therapeutic strategies to combat CSC resistance by targeting the various components of the CSC niche.