Current understanding of epigenetics mechanism as a novel target in reducing cancer stem cells resistance

Abstract

At present, after extensive studies in the field of cancer, cancer stem cells (CSCs) have been proposed as a major factor in tumor initiation, progression, metastasis, and recurrence. CSCs are a subpopulation of bulk tumors, with stem cell-like properties and tumorigenic capabilities, having the abilities of self-renewal and differentiation, thereby being able to generate heterogeneous lineages of cancer cells and lead to resistance toward anti-tumor treatments. Highly resistant to conventional chemo- and radiotherapy, CSCs have heterogeneity and can migrate to different organs and metastasize. Recent studies have demonstrated that the population of CSCs and the progression of cancer are increased by the deregulation of different epigenetic pathways having effects on gene expression patterns and key pathways connected with cell proliferation and survival. Further, epigenetic modifications (DNA methylation, histone modifications, and RNA methylations) have been revealed to be key drivers in the formation and maintenance of CSCs. Hence, identifying CSCs and targeting epigenetic pathways therein can offer new insights into the treatment of cancer. In the present review, recent studies are addressed in terms of the characteristics of CSCs, the resistance thereof, and the factors influencing the development thereof, with an emphasis on different types of epigenetic changes in genes and main signaling pathways involved therein. Finally, targeted therapy for CSCs by epigenetic drugs is referred to, which is a new approach in overcoming resistance and recurrence of cancer.

Dissecting Tumor Growth: The Role of Cancer Stem Cells in Drug Resistance and Recurrence

“…Besides different tumor compositions, the overlap in signaling pathways and cell interactions can generate a substantial phenotypic repertoire within niches and CSCs that is more complex when the tumor is more aggressive. CSCs show different transcriptional and epigenetic signatures to maintain the niches [ 108 , 109 , 110 , 111 , 112 , 113 , 114 , 115 , 116 ].…”

The paradigm of drug resistance in cancer: an epigenetic perspective

“…However, the epigenetic alternations are reversible and require to be actively maintained by epigenetic modifiers, making them an attractive target for therapeutic intervention. The current understanding of CSC epigenome provides new insights into targeted therapy by epigenetic drugs to overcome CSC drug resistance [ 173 ]. Several studies have utilized epigenome modifying drugs alone or combined with conventional treatments to modulate the epigenetic changes to attenuate drug resistance [ 174 ] ( Figure 2 ).…”

Epi‐immunotherapy for cancers: rationales of epi‐drugs in combination with immunotherapy and advances in clinical trials

“…On the other hand, the epigenetic alterations promote CSC self-renewal, proliferation and metastasis and confer treatment resistance [25][26][27][28] However, the best clinical responses to the combined treatment with DNMTi plus programmed cell death protein-1 (PD-1) blockade were found in those patients who received low-dose DNMTi regimens in which the drug dose would not result in cytotoxicity [7]. For example, in a patient tumor-derived xenograft model of colorectal cancer (CRC), low-dose DAC can re-modulate the TME to sensitize the PD-1 blockade [40].…”