Targeting Cancer Stem Cells as the Key Driver of Carcinogenesis and Therapeutic Resistance

Abstract

The emerging concept of cancer stem cells (CSCs) as the key driver behind carcinogenesis, progression, and diversity has displaced the prior model of a tumor composed of cells with similar subsequently acquired mutations and an equivalent capacity for renewal, invasion, and metastasis. This significant change has shifted the research focus toward targeting CSCs to eradicate cancer. CSCs may be characterized using cell surface markers. They are defined by their capacity to self-renew and differentiate, resist conventional therapies, and generate new tumors following repeated transplantation in xenografted mice. CSCs' functional capabilities are governed by various intracellular and extracellular variables such as pluripotency-related transcription factors, internal signaling pathways, and external stimuli. Numerous natural compounds and synthetic chemicals have been investigated for their ability to disrupt these regulatory components and inhibit stemness and terminal differentiation in CSCs, hence achieving clinical implications. However, no cancer treatment focuses on the biological consequences of these drugs on CSCs, and their functions have been established. This article provides a biomedical discussion of cancer at the time along with an overview of CSCs and their origin, features, characterization, isolation techniques, signaling pathways, and novel targeted therapeutic approaches. Additionally, we highlighted the factors endorsed as controlling or helping to promote stemness in CSCs. Our objective was to encourage future studies on these prospective treatments to develop a framework for their application as single or combined therapeutics to eradicate various forms of cancer.

Keywords: cancer; cancer stem cells; carcinogenesis; resistance; therapeutic.

Figure 1

Schematic representation of the stochastic and CSC models of carcinogenesis.

Figure 2

A diagrammatic representation of the microenvironment of a tumor highlighting the multiple cell phenotypes.

Figure 3

Schematic diagram summarizing the potential origins of CSCs.

Figure 4

Potential molecular mechanisms that contribute to intrinsic or acquired treatment resistance to conventional therapeutic approaches for various forms of cancer.

Figure 5

CSCs proliferate quickly via SRPs such as Nanog, Notch, Hedgehog, Wnt, and JAK/STAT dysregulation.

Figure 6

Schematic representation demonstrating that targeting CSCs’ quiescence is a promising approach to tackling drug resistance.

Figure 7

Schematic illustration revealing the various promising types of nanoparticles that contribute to nanoparticle-mediated targeted drug delivery to CSCs.