Section 5: Conclusions and perspectives (from DOI: 10.1038/s41392-020-0110-5)
From publication: "Targeting cancer stem cell pathways for cancer therapy" published as Signal Transduct Target Ther; 2020 ; 5 8; DOI: https://doi.org/10.1038/s41392-020-0110-5
Section 5: Conclusions and perspectives
We can conclude that CSCs are a small population of cancer cells that have self-renewal capacity and differentiation potential, thereby conferring tumor relapse, metastasis, heterogeneity, multidrug resistance, and radiation resistance. Several pluripotent transcription factors, including Oct4, Sox2, Nanog, KLF4, and MYC and some intracellular signaling pathways, including Wnt, NF-kappaB, Notch, Hh, JAK-STAT, PI3K/AKT/mTOR, TGF/Smad, and PPAR, as well as extracellular factors, including vascular niches, hypoxia, TAM, CAF, cancer-associated MSCs, the ECM, and exosomes, are essential regulators of CSCs. Drugs, vaccines, antibodies, and CAR-T cells targeting these pathways have also been developed to target CSCs. Importantly, many clinical trials on CSCs have also been performed and show a promising future for cancer therapy.
However, there are also multiple hurdles that need to be solved to effectively eliminate CSCs. First, the characteristics of many CSCs in specific types of tumors are not well identified. Second, since most studies on CSCs are performed in immune-deficient mice in the absence of an adaptive immune system, these models do not recapitulate the biological complexity of tumors in the clinic. Third, CSCs exist in a specific niche that sustains their survival. However, isolated CSCs are used in most current studies that lacks a microenvironment. Fourth, the environmental factors in CSC niches are not well understood, and the relationship between TAMs/CAFs and CSCs has not been well studied. Fifth, since CSCs also share some signaling pathways with normal stem cells, not all the regulatory factors that contribute to CSCs are appropriate for use as therapeutic targets in cancer treatment. Sixth, whether CSCs should be activated or arrested is an open question in cancer therapy. Seventh, novel signaling and more regulatory levels, such as RNA editing, epigenetics, and cellular metabolism, should be considered in cancer therapy because they also contribute to the stemness of CSCs. Eighth, some inhibitors that target CSC signaling are not very specific, and so new inhibitors need to be designed. Ninth, natural products that target CSCs should also be studied in the future. Finally, novel ways of targeting the microenvironment of CSCs are also promising and need to be explored.
<Footnote: These authors contributed equally: Liqun Yang, Pengfei Shi
