Cancer stem cells in glioblastoma – an update

Cancer arises due to genetic alterations, which allow cells to proliferate uncontrollably and acquire other features to become an invasive tumor. The rationale behind the traditional therapies is that they target rapidly proliferating tumor cells. However, these therapies have failed due to genetic and cellular heterogeneity, which allows a subpopulation of cancer cells to escape treatment resulting in cancer recurrence. Considerable evidence points to the existence of cancer stem-like cells (CSCs) that form a varying yet a minority fraction within tumors. The CSCs alone can initiate tumors in vivo and are responsible for therapy resistance, thus warranting more attention on their origin and biology. The process of tumor initiation by CSCs presumably involves, besides their self-renewal, differentiation into bulk cells (non-CSCs), which forms the basis of plasticity that arises due to epigenetic programming. Evidence indicates that non-CSCs reprogram to create CSCs, thus making the proportions of CSCs and non-CSCs highly dynamic in a given tumor. Transdifferentiation is another type of plasticity wherein, tumor cells or CSCs acquire features of different cell lineage like endothelial cells resulting in a more aggressive tumor. Understanding the mechanisms behind various forms of cellular plasticity may help develop novel strategies for treating cancer.