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INTERNATIONAL CONGRESS OF

PharmacoGenetics

• From Stem Cells to Tumors: The Epigenetic Control of Cancer Signaling Pathways

• Helia Sepahvand,¹ Majedeh Mortazavi,² Diana Sedaghatnia,³ Sarina Roshani,⁴ Narges Safari,^5,* Hesameddin Akbarein,⁶
  1. DVM Student, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  2. DVM Student, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  3. DVM Student, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  4. DVM Student, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran.
  5. DVM Student, Faculty of Veterinary Medicine, Garmsar Branch, Islamic Azad University, Garmsar, Iran.
  6. Division of Epidemiology & Zoonoses, Department of Food Hygiene & Quality Control, Faculty of Veterinary Medicine, University of Tehran, Tehran, Iran
  
  
  
• Introduction: It takes a lot of changes in genetic and epigenetic processes that control cell fate, proliferation, and differentiation for normal stem cells to turn into cancerous cells. One of the most important is epigenetic regulation, which controls which cancer signaling pathways are turned on and off without changing the DNA code underneath. Cancer research is now mainly focused on figuring out how epigenetic changes affect the growth of tumors. This has led to discoveries about how DNA methylation, histone modification, and non-coding RNAs affect the functions of cells that cause cancer to spread. This review discusses how epigenetic control affects cancer signaling pathways, focusing on how stem cells are controlled, how they turn into cancerous cells, and possible cancer therapies targeting epigenetic changes.
• Methods: This review utilized trustworthy articles published in databases such as Scopus, ScienceDirect, Google Scholar, ResearchGate, and PubMed. Library researches were also conducted. English keywords such as "epigenetic control," "stem cell," "tumors," and "cancer signaling" and chose the articles whose descriptions and full texts had similar words. No limitation of date and year of publications was included.
• Results: Cancer stem cells (CSCs) are cancerous cells that cause tumors to grow, become resistant to treatment, and return. Epigenetic changes, like DNA methylation, histone modifications, and non-coding RNA expression, are the significant ways they are made and kept up. These pathways manage critical signaling networks needed for CSCs to live and grow. They include Wnt/β-catenin, Hedgehog, Notch, and TGFβ/BMP. When these pathways are changed, they can set off feedback loops that help keep CSC stable but also cause cancer. The epigenome of cancer is unstable, and it changes even more with age, the surroundings, and mutations in epigenetic regulators. This instability changes the structure of chromatin and the links between enhancers and promoters. This changes how signaling pathways that keep CSC alive are controlled. Recent improvements in single-cell sequencing methods have made it possible for researchers to look into these epigenetic changes at a level of detail that has never been seen before. This has shown how complicated tumor heterogeneity is and helped them find the epigenetic changes that support pathways that are driven by CSCs. How things are done now suggests that finding new biomarkers and making specific medicines that mess up epigenetic regulation in cancer might be possible. These methods might help treatments work better by focusing on epigenetic changes that support the survival of CSCs and the growth of tumors. Cells and stem cells share the same functions, like the ability to divide and make new cells. But cancer cells take over these control systems, which lets them multiply out of control and form tumors. Epigenetic processes, like DNA methylation and histone change, are essential for keeping the balance between dividing and growing stem cells. In cancer, these epigenetic factors are often changed, which sets off signaling pathways that help tumors grow. Epigenetic mechanisms tightly control several essential signaling pathways that play a role in cancer development. These include the Wnt, Notch, Hedgehog, and PI3K/AKT/mTOR pathways. Changes in epigenetics that affect the activity or production of parts in these pathways can cause cells to grow out of control, become resistant to apoptosis, and spread to other body parts. Since epigenetic changes play a big part in controlling cancer signaling pathways, more and more people are interested in making epigenetic treatments that target these changes.
• Conclusion: Epigenetic mechanisms are essential for both standard and abnormal development. Chemical changes in the epigenome, like histone modifications and DNA methylation, are significant for stem cells to differentiate and become different tissue types. The best way to treat various types of cancer is to use non-responsive, inactive cancer stem cells. These cells stay dormant for long periods and become active again when the cancer has spread. Figuring out how these changes affect the growth of cancer has led to new ways of creating epigenetic treatments that target the molecular processes that cause cancer. As the studies go further, focusing on the epigenetic regulators of cancer signaling pathways could lead to new ways to treat and control cancer and improve patients’ clinical situation.
• Keywords: Epigenetic Control, Stem Cell, Tumors and Cancer Signaling