Regulation and signaling pathways in cancer stem cells: implications for targeted therapy for cancer

Abstract

Cancer stem cells (CSCs), initially identified in leukemia in 1994, constitute a distinct subset of tumor cells characterized by surface markers such as CD133, CD44, and ALDH. Their behavior is regulated through a complex interplay of networks, including transcriptional, post-transcriptional, epigenetic, tumor microenvironment (TME), and epithelial-mesenchymal transition (EMT) factors. Numerous signaling pathways were found to be involved in the regulatory network of CSCs. The maintenance of CSC characteristics plays a pivotal role in driving CSC-associated tumor metastasis and conferring resistance to therapy. Consequently, CSCs have emerged as promising targets in cancer treatment. To date, researchers have developed several anticancer agents tailored to specifically target CSCs, with some of these treatment strategies currently undergoing preclinical or clinical trials. In this review, we outline the origin and biological characteristics of CSCs, explore the regulatory networks governing CSCs, discuss the signaling pathways implicated in these networks, and investigate the influential factors contributing to therapy resistance in CSCs. Finally, we offer insights into preclinical and clinical agents designed to eliminate CSCs.

Dysregulation of the p53 pathway provides a therapeutic target in aggressive pediatric sarcomas with stem-like traits

“…Strikingly, knockdown of SOX2 limited but not completely suppressed stemness of mut-p53 sarcoma cells, suggesting that p53 alteration is important for development of fully stem-like phenotype in sarcomas. Moreover, after successful SOX2 knockdown, we observed upregulation of NANOG and KLF4 transcription factors (both associated with cancer stemness [45,46]) in MNNG/HOS and ESFT-15 cell lines, respectively. These outcomes contrast with expectations based on prior studies, which suggested that downregulation of SOX2 reduces NANOG expression [47] and decreases the stability of KLF4 [48].…”

Ratiometric Near-Infrared Fluorescent Probe Monitors Ferroptosis in HCC Cells by Imaging HClO in Mitochondria

“…The resulting residue was then purified through separation using ACM/MeOH (50:1 to 10:1, v/v) and eluted to yield a dark blue solid of Mito-Rh-S (536.14 mg, 63.15%). 1 a low detection limit, (2) rapid response time, (3) ratiometric detection capability, (4) emission in the near-infrared range, and (5) targeted delivery to the mitochondria. 37,38 The selected cationic rhodamine moiety serves as an optimal fluorophore, combining the benefits of nice water solubility and mitochondrial targeting ability.…”

“…Ferroptosis is an iron-dependent programmed cell death that is characterized by the dysregulation of lipid reactive oxygen species (ROS) production, among which hypochlorous acid (HClO) could be recognized as a potential biomarker for detecting ferroptosis. − Hepatocellular carcinoma (HCC) is a prevalent malignant disease with a significant mortality rate, and it is closely associated with the overexpression of ROS during pathological progression . Additionally, a large number of studies have demonstrated the pivotal iron overload-induced oxidative stress injury in this process .…”

Transformation of an olfactory placode-derived cell into one with stem cell characteristics by disrupting epigenetic barriers

“…There are alternative interpretations not yet dismissed, such as the formation of a rogue population of cells that misregulated developmentally associated gene sets in a disorganized way and without proper regulation of the associated gene networks. For example, certain types of tumor cells exhibit global gene misregulation (Fabregat, 2009;Lee and Young, 2013;Zhang and Manley, 2013), including misregulation of stem-cell genes (Nairuz et al, 2023;Zeng et al, 2023). While we have not conducted a full set of experiments to more rigorously investigate tumor properties of OP6 colonies, we do note that these colonies exhibited sensitivity to surrounding cell crowding, thus would seem to retain attributes of contact inhibition (McClatchey and Yap, 2012), and had not attained mitotic independence nor more extreme enhancement of doubling times; these observations suggest more organized as opposed to disorganized growth characteristics.…”