Discovery of the cancer stem cell related determinants of radioresistance

Abstract

Tumors are known to be heterogeneous containing a dynamic mixture of phenotypically and functionally different tumor cells. The two concepts attempting to explain the origin of intratumor heterogeneity are the cancer stem cell hypothesis and the clonal evolution model. The stochastic model argues that tumors are biologically homogenous and all cancer cells within the tumor have equal ability to propagate the tumor growth depending on continuing mutations and selective pressure. By contrast, the stem cells model suggests that cancer heterogeneity is due to the hierarchy that originates from a small population of cancer stem cells (CSCs) which are biologically distinct from the bulk tumor and possesses self-renewal, tumorigenic and multilineage potential. Although these two hypotheses have been discussed for a long time as mutually exclusive explanations of tumor heterogeneity, they are easily reconciled serving as a driving force of cancer evolution and diversity. Recent discovery of the cancer cell plasticity and heterogeneity makes the CSC population a moving target that could be hard to track and eradicate. Understanding the signaling mechanisms regulating CSCs during the course of cancer treatment can be indispensable for the optimization of current treatment strategies.

An Epigenetic Reprogramming Strategy to Resensitize Radioresistant Prostate Cancer Cells

“…However, development of therapeutic agents eradicating CSCs remains challenging due to the high diversity and plasticity of CSC phenotypes. Recent advances in DNA sequencing allowing global analysis of genetic landscape in individual tumor cells revealed a high heterogeneity of different subclones within the same tumor specimens and has provided an insight into the subclonal evolution, suggesting that CSCs and clonal evolution models are not mutually exclusive (15,31). Furthermore, evolved CSCs that survive after chemo-or radiotherapy might confer treatment resistance.…”

Aldehyde Dehydrogenase Is Regulated by β-Catenin/TCF and Promotes Radioresistance in Prostate Cancer Progenitor Cells

“…Nevertheless, some patients with high-risk prostate cancer develop local relapse after radiation therapy. The most obvious explanation for radiotherapy failure is related to the CSC population, which was not completely sterilized during the treatment and caused tumor recurrence (6,7).…”

The Role of Biomaterials on Cancer Stem Cell Enrichment and Behavior

“…They can help promote properties such as cell self-renewal, migration, release of endocrine and paracrine factors that regulate tumor development and angiogenesis, form hypoxic niches, and increase therapy resistance. 44 Accumulating evidence also indicates that cancer cells in 3D culture display higher malignancy and invasive capability compared to their counterparts in two-dimensional (2D) culture, which has been linked to increased cancer cell stemness. 45 Consequently, a number of polymers have been utilized to develop 3D cell culture scaffolds for the investigation of proliferation, growth and migration of CSCs.…”