Signaling pathways in the regulation of cancer stem cells and associated targeted therapy

Abstract

Cancer stem cells (CSCs) are defined as a subpopulation of malignant tumor cells with selective capacities for tumor initiation, self‐renewal, metastasis, and unlimited growth into bulks, which are believed as a major cause of progressive tumor phenotypes, including recurrence, metastasis, and treatment failure. A number of signaling pathways are involved in the maintenance of stem cell properties and survival of CSCs, including well‐established intrinsic pathways, such as the Notch, Wnt, and Hedgehog signaling, and extrinsic pathways, such as the vascular microenvironment and tumor‐associated immune cells. There is also intricate crosstalk between these signal cascades and other oncogenic pathways. Thus, targeting pathway molecules that regulate CSCs provides a new option for the treatment of therapy‐resistant or ‐refractory tumors. These treatments include small molecule inhibitors, monoclonal antibodies that target key signaling in CSCs, as well as CSC‐directed immunotherapies that harness the immune systems to target CSCs. This review aims to provide an overview of the regulating networks and their immune interactions involved in CSC development. We also address the update on the development of CSC‐directed therapeutics, with a special focus on those with application approval or under clinical evaluation.

NRF2 signaling plays an essential role in cancer progression through the NRF2-GPX2-NOTCH3 axis in head and neck squamous cell carcinoma

“…Aberrant activation of pathways regulating stem cell selfrenewal, such as Notch, Hedgehog (HH), and Wnt, are also pivotal in the tumorigenic potential of CSCs [44]. Dysregulation of these pathways contributes to drive tumor progression [55]. We examined all three signaling pathways and found that Notch signaling was disrupted in GPX2 depletion HNSCC cells, especially NOTCH3.…”

URB2 as an important marker for glioma prognosis and immunotherapy

“…There are a large number of previous studies on TGF beta signaling pathway. Studies have shown that the TGF-beta signaling pathway has different roles in the different stages of human cancer progression (Manni and Min, 2020;Baba et al, 2022). TGF-beta acts as a cancer suppressor in the initial stage of tumorigenesis (de Caestecker et al, 2000;Zhang et al, 2017;Chandra Jena et al, 2021).…”

Role of circular RNAs in lung cancer

“…However, the complexity of immune cell heterogeneity across cell types poses challenges in precisely understanding CSC-immune cell interactions. Recently, the widespread use of single-cell RNA sequencing has enabled the identification of changing states in both CSCs and immune cells, shedding light on their interactions in different tumor contexts ( Manni and Min, 2022 ). Further investigation is needed to explore the communication among these immune cells within the tumor microenvironment (TME), with the aim of advancing the development of immunotherapies that specifically target cancer stem cells (CSCs) more effectively.…”