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Review
. 2022 Sep 20:2:1011882.
doi: 10.3389/fmmed.2022.1011882. eCollection 2022.

Targeting epigenetic alterations in cancer stem cells

Verona F  1 , Pantina V D  2 , Modica C  2 , Lo Iacono M  1 , D'Accardo C  1 , Porcelli G  1 , Cricchio D  2 , Turdo A  1 , Gaggianesi M  2 , Di Franco S  2 , Todaro M  1 , Veschi V  2 , Stassi G  2
Affiliations
Review

Targeting epigenetic alterations in cancer stem cells

Verona F et al. Front Mol Med. .

Abstract

Oncogenes or tumor suppressor genes are rarely mutated in several pediatric tumors and some early stage adult cancers. This suggests that an aberrant epigenetic reprogramming may crucially affect the tumorigenesis of these tumors. Compelling evidence support the hypothesis that cancer stem cells (CSCs), a cell subpopulation within the tumor bulk characterized by self-renewal capacity, metastatic potential and chemo-resistance, may derive from normal stem cells (NSCs) upon an epigenetic deregulation. Thus, a better understanding of the specific epigenetic alterations driving the transformation from NSCs into CSCs may help to identify efficacious treatments to target this aggressive subpopulation. Moreover, deepening the knowledge about these alterations may represent the framework to design novel therapeutic approaches also in the field of regenerative medicine in which bioengineering of NSCs has been evaluated. Here, we provide a broad overview about: 1) the role of aberrant epigenetic modifications contributing to CSC initiation, formation and maintenance, 2) the epigenetic inhibitors in clinical trial able to specifically target the CSC subpopulation, and 3) epigenetic drugs and stem cells used in regenerative medicine for cancer and diseases.

Keywords: cancer stem cells; epigenetic alterations; epigenetic inhibitors; normal stem cells; regenerative medicine.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Epigenetic alterations responsible for the initiation and maintenance of cancer stem cells (CSCs). An aberrant epigenetic reprogramming plays a critical role in CSC initiation and maintenance, driving the transformation process of a normal stem cell (NSC) versus a cancer stem cell (CSC). The principal alterations involving the epigenetic regulators that sustain the formation (left) and the maintenance (right) of this aggressive subpopulation are indicated along with the functions/properties of CSCs that these enzymes are promoting.
FIGURE 2
FIGURE 2
Epigenetic therapy using NSCs in regenerative medicine and targeting CSCs in tumors (left) Epigenetically engineered adult normal stem cells (NSCs) or induced pluripotent stem cells (iPSCs) represent an innovative and promising tool in regenerative medicine. Adult stem cells deriving from damaged tissue or iPSCs could be reprogrammed using the indicated epigenetic drugs in order to obtain a specific lineage commitment, thus allowing tissue repair and regeneration. (right) On the other hand, the use of epigenetic inhibitors in cancer therapy targeting the aberrant epigenetic modifications responsible for CSC initiation and maintenance may lead to a reduction of tumor mass by inhibiting the stemness features of CSC subpopulation.
See this image and copyright information in PMC

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