Metastasis, recurrence, heterogeneity, resistance to chemotherapy and radiotherapy, and avoiding immunological surveillance are the primary causes of cancer treatment failure. The traits of cancer stem cells (CSCs) could be the cause of all these failures. Due to their capacity to arrest in the G0 phase, which results in the formation of fresh tumors, CSCs can lead to cancer spread, cancer relapse, multidrug resistance, and radiation resistance. CSCs may therefore be thought of as the most promising cancer therapeutic targets.
Through self-renewal and differentiation into several cellular subtypes, CSCs can become malignancies. Numerous intracellular and extracellular variables that can be utilized as therapeutic targets for cancer treatment regulate the activity of CSCs. We outlined CSCs' properties, techniques for locating and isolating them, regulatory frameworks, and current research on CSC targeting for cancer therapy, including both basic and applied research.
However, there are also a number of problems that must be resolved before CSCs can be effectively eliminated:
1. It is difficult to pinpoint the characteristics of many CSCs found in particular kinds of malignancies.
2. These models do not accurately represent the molecular complexity of malignancies in the clinic because the majority of CSC research are conducted in immuno-deficient mice without an adaptive immune system.
3. CSCs are able to survive because they fill a specific niche. However, the majority of recent research that lack a microenvironment use isolated CSCs.
4. The relationship between TAMs/CAFs and CSCs has not been thoroughly researched, and environmental elements in CSC niches are little known.
5. Not all of the regulatory factors that contribute to CSCs are appropriate for use as therapeutic targets in cancer treatment because CSCs and normal stem cells share some signaling pathways. 6. In terms of cancer therapy, it is unclear whether CSCs should be activated or arrested.
7. Because they also contribute to the stemness of CSCs, new signaling and additional regulatory levels, such as RNA editing, epigenetics, and cellular metabolism, should be taken into account in cancer therapy.
8. Current CSC signaling inhibitors lack sufficient specificity, necessitating the development of novel inhibitors.
9. Future research should also focus on natural compounds that target CSCs. The microenvironment of CSCs can be targeted in unique ways, which should be investigated.
Reference: Yang, L., Shi, P., Zhao, G. et al. Targeting cancer stem cell pathways for cancer therapy. Sig Transduct Target Ther 5, 8 (2020). https://doi.org/10.1038/s41392-020-0110-5
