Int J Stem Cells.  2021 Nov;14(4):386-399. 10.15283/ijsc21084.

Targeting Cancer Stem Cell Markers or Pathways: A Potential Therapeutic Strategy for Oral Cancer Treatment

• Lee JW
• Lee HY

• KMID: 2522558
• DOI: http://doi.org/10.15283/ijsc21084

Abstract

Cancer stem cells (CSCs) are a small subset of cancer cells with stem cell-like properties, self-renewal potential, and differentiation capacity into multiple cell types. Critical genetic alterations or aberrantly activated signaling pathways associated with drug resistance and recurrence have been observed in multiple types of CSCs. In this context, CSCs are considered to be responsible for tumor initiation, growth, progression, therapeutic resistance, and metastasis. Therefore, to effectively eradicate CSCs, tremendous efforts have been devoted to identify specific target molecules that play a critical role in regulating their distinct functions and to develop novel therapeutics, such as proteins, monoclonal antibodies, selective small molecule inhibitors, and small antisense RNA (asRNA) drugs. Similar to other CSC types, oral CSCs can be characterized by certain pluripotency-associated markers, and oral CSCs can also survive and form 3D tumor spheres in suspension culture conditions. These oral CSC-targeting therapeutics selectively suppress specific surface markers or key signaling components and subsequently inhibit the stem-like properties of oral CSCs. A large number of new therapeutic candidates have been tested, and some products are currently in the pre-clinical or clinical development phase. In the present study, we review new oral CSC-targeted therapeutic strategies and discuss the various specific CSC surface markers and key signaling components involved in the stem-like properties, growth, drug resistance, and tumorigenicity of oral CSCs.

Keyword

Cancer stem cells; Stem cell-like characteristics; Drug resistance; Recurrence

Figure

• 

  Fig. 1 Schematic diagram summarizing the therapeutic strategies targeting oral CSCs. The diverse phenotypic heterogeneity and plasticity among cancer cells in bulk tumors have been explained by the CSC model of hierarchically organized tumors. Unlike bulk tumor cells, CSCs are intrinsically resistant to the majority of conventional chemotherapeutic agents; thus, the remaining CSC subpopulation can subsequently reconstitute tumors in patients with cellular heterogeneity.

• 

  Fig. 2 Schematic diagram summarizing the therapeutic strategies targeting oral CSC-specific surface markers or signaling pathways. Therapeutic efficiency could be enhanced by selectively targeting subtle expression differences in surface markers and alterations in various signaling regulators between CSC subpopulations and non-CSC subpopulations. For this reason, CSC markers can be used to identify CSC-enriched subpopulations and various therapeutic approaches effectively inhibit oral CSCs by targeting pluripotency-associated genes (ALDHs, CD44, CD133, and CD177) and CSC-specific signaling pathways (Wnt/β-catenin, Notch, and hedgehog signaling pathways).

Reference

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