Targeting self-renewal pathways in cancer stem cells: clinical implications for cancer therapy.

A Borah,D S Kumar,T Maekawa,A Rochani,S Raveendran

doi:10.1038/oncsis.2015.35

Abstract

Extensive cancer research in the past few decades has identified the existence of a rare subpopulation of stem cells in the grove of cancer cells. These cells are known as the cancer stem cells marked by the presence of surface biomarkers, multi-drug resistance pumps and deregulated self-renewal pathways (SRPs). They have a crucial role in provoking cancer cells leading to tumorigenesis and its progressive metastasis. Cancer stem cells (CSCs) are much alike to normal stem cells in their self-renewal mechanisms. However, deregulations in the SRPs are seen in CSCs, making them resistant to conventional chemotherapeutic agents resulting in the tumor recurrence. Current treatment strategies in cancer fail to detect and differentiate the CSCs from their non-tumorigenic progenies owing to absence of specific biomarkers. Now, it has become imperative to understand complex functional biology of CSCs, especially the signaling pathways to design improved treatment strategies to target them. It is hopeful that the SRPs in CSCs offer a promising target to alter their survival strategies and impede their tumorigenic potential. However, there are many perils associated with the direct targeting method by conventional therapeutic agents such as off targets, poor bioavailability and poor cellular distribution. Recent evidences have shown an increased use of small molecule antagonists directly to target these SRPs may lead to severe side-effects. An alternative to solve these issues could be an appropriate nanoformulation. Nanoformulations of these molecules could provide an added advantage for the selective targeting of the pathways especially Hedgehog, Wnt, Notch and B-cell-specific moloney murine leukemia virus integration site 1 in the CSCs while sparing the normal stem cells. Hence, to achieve this goal a complete understanding of the molecular pathways corroborate with the use of holistic nanosystem (nanomaterial inhibition molecule) could possibly be an encouraging direction for future cancer therapy.

Highlights

Cancer remains one of the deadliest diseases affecting large number of people worldwide every year
In the past decade, underlying cause discovered to be associated with tumor recurrence, metastasis and chemoresistance are a relatively small population of stem cells inhabiting each adult tissue called as the cancer stem cells (CSCs)
These stem cells in the long run have the opportunity to accumulate the mutations required for malignant transformation owing to their unlimited division potential. These cells were first identified by Bonnet and Dick (1997)[1] in acute myeloid leukemia and following their findings many other groups have identified these cells in various solid tumors of brain,[2] breast,[3] pancreas,[4] prostate[5,6] to name a few