• Cancer Stem Cells and Therapeutic Implications Review Article
  • Nora Arabbaraghi,1 Saman Hakimian,2,*
    1. Department of Cellular & Molecular Biology, Faculty of Advance Science & Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
    2. Department of Microbiology, Faculty of Advance Science & Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran


  • Introduction: Cancer, a complex and multifaceted disease, has been the subject of extensive research and investigation for centuries. Over the years, our understanding of cancer has evolved significantly, leading to breakthroughs in diagnosis, treatment, and prevention. One area of particular interest is the concept of cancer stem cells (CSCs), which has gained prominence in recent decades. The concept of stemness in cancer can be traced back to the mid-19th century when the first theory on the embryonic origin of cancer was formulated. It was not until the mid-20th century that significant progress was made in understanding cancer stem cells through studies on embryonal carcinoma cells. These early studies laid the foundation for the current cancer stem cell theory, which postulates that tumor growth is supported by a small fraction of tumoral cells that possess stem-like properties. In recent years, there has been a growing body of evidence challenging and expanding our understanding of CSCs. It is now recognized that intratumor heterogeneity plays a crucial role in cancer progression and treatment response. Intratumor heterogeneity refers to the presence of diverse subpopulations of cancer cells within a tumor, each with distinct genotypes and phenotypes. This heterogeneity arises from genetic mutations, epigenetic modifications, and interactions with the tumor microenvironment. Cancer stem cells are a subset of cells within a tumor that exhibit self-renewal capacity and the ability to differentiate into various cell types found within the tumor. These cells are thought to be responsible for tumor initiation, maintenance, and resistance to therapy. CSCs have been identified in various types of cancer, including breast cancer, leukemia, brain tumors, and colorectal cancer, among others. Understanding the mechanisms underlying intratumor heterogeneity and CSC biology is crucial for the development of effective cancer therapies. Recent studies have highlighted the role of epigenetic mechanisms in driving phenotypic differences between CSCs and non-CSCs. Epigenetic changes, such as DNA methylation and histone modifications, can alter gene expression patterns and contribute to the maintenance of CSC properties.
  • Methods: The discovery of CSC-specific biomarkers has also opened up new avenues for targeted therapies. By identifying and targeting specific surface markers or signaling pathways expressed by CSCs, researchers aim to selectively eliminate these cells and disrupt tumor growth. Additionally, novel therapeutic strategies have emerged that focus on modulating the tumor microenvironment to inhibit CSC activity and sensitize tumors to conventional treatments. Immunotherapy, which harnesses the body's immune system to recognize and destroy cancer cells, has shown promising results in targeting CSCs. By stimulating an immune response against CSC-specific antigens, immunotherapy holds the potential to eradicate CSCs and prevent tumor recurrence. Furthermore, advancements in gene therapy techniques offer the possibility of directly targeting CSCs by delivering therapeutic genes or RNA molecules specifically to these cells. Combination therapies that target both CSCs and non-CSCs have also gained attention as a strategy to overcome treatment resistance and improve patient outcomes. By simultaneously targeting multiple pathways involved in tumor growth and maintenance, these combination approaches aim to achieve more comprehensive and durable responses.
  • Results: Combination therapies that target both CSCs and non-CSCs have also gained attention as a strategy to overcome treatment resistance and improve patient outcomes. By simultaneously targeting multiple pathways involved in tumor growth and maintenance, these combination approaches aim to achieve more comprehensive and durable responses. In conclusion, the study of cancer stem cells and intratumor heterogeneity has revolutionized our understanding of cancer biology and treatment. The recognition that CSCs play a crucial role in tumor initiation, maintenance, and therapy resistance has opened up new avenues for targeted therapies.
  • Conclusion: Advances in epigenetics, biomarker discovery, immunotherapy, gene therapy, and combination therapies hold great promise for improving patient outcomes and transforming cancer treatment into a more personalized and effective approach. Continued research into CSC biology and intratumor heterogeneity will undoubtedly lead to further breakthroughs in our fight against cancer.
  • Keywords: cancer stem cells, stem cell therapy, resistance to therapy, tumor heterogeneity