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Review
. 2024 May 10:14:1404628.
doi: 10.3389/fonc.2024.1404628. eCollection 2024.

The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies

Oluwaseun Adebayo Bamodu  1   2 , Chen-Chih Chung  3   4   5 , Thomas R Pisanic 2nd  6   7   8 , Alexander T H Wu  9   10   11   12
Affiliations
Review

The intricate interplay between cancer stem cells and cell-of-origin of cancer: implications for therapeutic strategies

Oluwaseun Adebayo Bamodu et al. Front Oncol. .

Abstract

Background: Cancer stem cells (CSCs) have emerged as pivotal players in tumorigenesis, disease progression, and resistance to therapies.

Objective: This comprehensive review delves into the intricate relationship between CSCs and the cell-of-origin in diverse cancer types.

Design: Comprehensive review of thematically-relevant literature.

Methods: We explore the underlying molecular mechanisms that drive the conversion of normal cells into CSCs and the impact of the cell-of-origin on CSC properties, tumor initiation, and therapeutic responses. Moreover, we discuss potential therapeutic interventions targeting CSCs based on their distinct cell-of-origin characteristics.

Results: Accruing evidence suggest that the cell-of-origin, the cell type from which the tumor originates, plays a crucial role in determining the properties of CSCs and their contribution to tumor heterogeneity.

Conclusion: By providing critical insights into the complex interplay between CSCs and their cellular origins, this article aims to enhance our understanding of cancer biology and pave the way for more effective and personalized cancer treatments.

Keywords: cancer stem cells; cancer therapeutics; cell-of-origin; personalized medicine; therapy resistance; tumor heterogeneity; tumor microenvironment; tumorigenesis.

PubMed Disclaimer

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
A visual summary showing that normal tissue stem/progenitor cells give rise to CSCs, which then interact with and reshape the surrounding tumor microenvironment. This illustrates the critical interplay between cell-of-origin, CSCs, and the TME in cancer.
Figure 2
Figure 2
Origin and therapeutic targeting of CSCs. Normal tissue stem cells accumulate genetic and epigenetic alterations over time leading to dysregulation of signaling pathways such as Wnt, Hedgehog (HH), STAT3, and AKT. This results in aberrant stem cell processes and the transformation into CSCs with acquired self-renewal and tumor-initiating capabilities. CSCs drive tumor heterogeneity, metastasis, chemotherapy resistance, and relapse. Targeting dysregulated CSC signaling pathways provides a potential therapeutic approach to eliminate this tumorigenic population and improve patient outcomes.
Figure 3
Figure 3
An updated timeline of key discoveries related to cancer stem cell research.
See this image and copyright information in PMC

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