• A new approach to reversing resistance to therapies by targeting cancer stem cells: signaling , mechanisms, and potential agents
  • Soroush Partovi Moghaddam,1 Erfan shapourgan,2 Ashkan Hajjafari,3 Soheil Sadr,4 Hassan Borji,5,*
    1. Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
    2. Department of medicine, Tehran university of medical science
    3. Department of Clinical Sciences, Faculty of Veterinary Medicine, Science and Research Branch, Islamic Azad University, Tehran, Iran
    4. Department of Clinical Sciences, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad, Mashhad, Iran
    5. Department of Pathobiology, Faculty of Veterinary Medicine, Ferdowsi University of Mashhad


  • Introduction: The ability of cancer stem cells (CSCs) to self-renew and differentiate is an important factor that contributes to tumor progression and resistance to therapies. In spite of this, it remains unclear as to how the underlying processes work. By understanding the key characteristics and the mechanism of resistance of CSCs, it may be possible to improve patient outcomes and reduce the likelihood of relapse in the future. A clinical perspective was presented in this review, which highlights CSC identification, intrinsic and extrinsic mechanisms of therapy resistance within CSCs, signaling pathways within CSCs that contribute to loss of responsiveness to treatment, along with possible CSC-targeting agents for various types of cancer.
  • Methods: There was an extensive research effort conducted between the years 2000 and 2020 to target cancer stem cells and address the issue of therapy resistance in the treatment of cancer. The aim of this study is to retrieve pertinent studies that have been published during the period of time under discussion, by searching reputable databases such as Scopus, PubMed, Science Direct, and Google Scholar. As part of the search strategy, we aimed at identifying literature located on mechanisms, potential agents and signaling pathways that may be able to reverse therapy resistance in CSCs using their mechanisms and signaling pathways. A particular set of keywords were used to identify the research, which included "cancer stem cells," "therapy resistance mechanisms," "signaling pathways in CSCs," and "novel therapeutic agents." The original 10,000 studies that were identified were screened based on abstracts, with 9700 being excluded based on abstracts, leaving 300 studies for review in full. In order to perform a comprehensive review of all the articles that were considered relevant to this study, a rigorous screening process was conducted. The objective of this study was to shed light on the complex mechanisms that underlie therapy resistance in CSCs and identify potential agents that might provide new approaches to the treatment of cancer.
  • Results: There are a variety of types of cancer that can be treated by targeting their cancer stem cells in order to overcome therapy resistance. Throughout the past few years, there has been an increasing focus on identifying potential agents that can reduce CSC resistance, as well as unraveling the signaling pathways involved in CSC-driven resistance. The results of this study have shown that CSCs play a critical role in the resistance to treatment as a result of this study. There is growing evidence to suggest that CSCs can survive conventional cancer treatments due to their self-renewal ability and multidrug resistance. As a result, conventional cancer treatments fail. A number of key mechanisms have been discovered by researchers over the last few years. It has been demonstrated that several signaling pathways play a role in regulating the maintenance and resistance of CSCs, including Notch, Wnt, and Hedgehog. Several studies have shown that targeting these pathways is effective in stimulating the response of CSCs to therapy when they are targeted. There have been many compounds tested in preclinical and clinical trials in order to determine if they could serve as potential agents in the future. Inhibitors of small molecule receptors, monoclonal antibodies, and natural compounds have been shown to be effective in selectively targeting CSCs. Several preclinical studies have shown that CD44 inhibitors, ALDH inhibitors, and specific kinase inhibitors have demonstrated encouraging results in preclinical studies.
  • Conclusion: A better understanding of the mechanisms underlying CSC-mediated resistance to therapy, as well as the identification of potential agents that can target CSCs, is crucial to improve cancer treatment outcomes and overcome resistance difficulties. It is imperative to build an understanding of the mechanisms that underlie CSC-mediated resistance to therapy. There is promise in these efforts for enhancing the efficacy of future cancer therapies.
  • Keywords: Cancer stem cells Resistance potential agent mechanism cancer treatment