Journal of Carcinogenesis & Mutagenesis

Abstract

Radioresistance and Cancer Stem Cells: Survival of the Fittest

Lei Sun, Stephanie M Cabarcas and William L Farrar

Cancer arises from the accumulation of genetic mutations and aberrant epigenetic modifications in normal cells. Cancer stem cells (CSCs) have been described as a unique tumorigenic population of cells within the tumor mass that have the ability to self-renew and differentiate. In the past few years, the existence and nature of CSCs has served as one of the most controversial topics in the field of cancer biology; however, more recently, there is an abundant amount of evidence that demonstrates their existence. CSCs are believed to be responsible for resistance against conventional therapies, such as radiotherapy that contributes to uncontrolled tumor growth, metastasis and subsequently, patient demise. In this review, we summarize the mechanism(s) by which CSCs are radioresistant, including their enhanced DNA damage response, cell cycle status and the role of the CSC niche. Moreover, by using the Oncomine database, we display data from our laboratory and other groups demonstrating that CSCs have an increased expression of radioresistance genes, which are also involved in carcinogenesis, metastasis and patient relapse. In addition, we provide data from prostatospheres derived from primary patient cells demonstrating that the RAN signaling pathway is one of the top upregulated pathways within the CSC population. Therefore, we hypothesize that the RAN signaling pathway is related to the radioresistance property of CSCs. We briefly review this burgeoning field of study on the biological behavior of CSCs and provide new suggestions for the development of future therapies to target radioresistant CSCs in both pharmaceutical investigations and clinical trials.