INTERNATIONAL CONGRESS OF
CancerGenetics
An overview of Cancer stem cells: from origin to therapeutic implications
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Nora Arabbaraghi,1,*
1. Department of cellular and molecular biology, Faculty of Advance Science & Technology, Tehran Medical Science, Islamic Azad University, Tehran, Iran
- Introduction: The link between cancer and stemness has a deep-rooted history, which is summarized here. It started in the mid-19th century with the first theory about the embryonic origins of cancer and progressed through studies on embryonal carcinoma cells in the mid-20th century. This journey has culminated in the modern cancer stem cell theory, which proposes that a small group of tumor cells with stem-like traits drives tumor growth. However, over the last fifteen years, various studies have consistently urged a reassessment of the cancer stem cell paradigm. Cancer stem cells (CSCs), also known as tumor-initiating cells (TICs), are characterized as cells that can sustain themselves through self-renewal. They demonstrate a high level of resistance to current treatment strategies and are a key cause of cancer relapse.
- Methods: Cancer stem cells (CSCs) are self-renewing cell types found in various liquid and solid tumors, playing a role in tumor initiation, growth, resistance, recurrence, and metastasis following treatment. The identification of CSCs relies on the expression of specific cell surface markers, which vary by tumor type. There is a dynamic interaction between CSCs, cancer cells, and non-CSCs, influenced by signals from both CSCs and the tumor microenvironment (TME), including the CSC niche. Among the most significant cells in this process are cancer-associated fibroblasts, which facilitate both the differentiation of CSCs and the dedifferentiation of non-CSCs, leading to a CSC-like phenotype. It is widely accepted that cancer stem cells (CSCs) serve as the primary "seeds" for tumor initiation, development, metastasis, and recurrence. CSCs have evolved and exhibit significant heterogeneity. For instance, breast CSCs display varying patterns of surface biomarkers, such as CD44+, CD24−, SP, and ALDH+. Additionally, melanoma stem cells, whether CD271− or CD271+, are capable of forming tumors in SCID mice. This heterogeneity has also been observed in other cancers, including glioblastoma, prostate cancer, and lung cancer. The complexity of CSC heterogeneity highlights the need for more effective biomarkers to accurately identify CSCs and differentiate between their various subtypes. Stem cell niches are specialized regions within tissues that create specific microenvironments to support and enhance the self-renewal capacity of cancer stem cells (CSCs) and their ability to produce differentiated progeny. The concept of the stem cell niche was initially introduced by Schofield, who showed that successful transplants could only occur when stem cells were sourced from the bone marrow. He also suggested that the stem cell niche plays a crucial role in determining stem cell fate, as the behavior of stem cells is shaped by their interactions with other cells in the niche. Cancer stem cells (CSCs) are known to contribute to prolonged tumor growth, the spread of cancer to distant organs, and the eventual recurrence of the disease following chemotherapy and/or radiotherapy. These cells exhibit a gene signature associated with epithelial-mesenchymal transition (EMT), which is linked to their ability to proliferate and migrate to remote locations. Furthermore, DNA mutations and factors within the tumor microenvironment (TME) may influence CSCs, pushing them toward a metastatic phenotype.
- Results: Given their resistance to traditional cancer treatments, cancer stem cells (CSCs) have led to the exploration of various alternative strategies, such as immunotherapy, gene therapy, molecular inhibition, and combination therapies. Immunotherapy, in particular, holds significant potential for targeting CSCs. For example, vaccines that incorporate antigens from CD133+ hepatocellular carcinoma cells can stimulate specific cytotoxic lymphocytes, thereby effectively eliminating CSCs associated with hepatocellular carcinoma. Radiotherapy (RT) continues to be a viable treatment option for various cancers. Advances in medical imaging and dose delivery technology have paved the way for three-dimensional conformal treatment. Standard RT is based on five radiobiological principles: DNA damage repair, cell redistribution during the cell cycle, repopulation, reoxygenation of hypoxic tumor regions, and radiosensitivity—collectively referred to as the "5 Rs" of radiobiology. The goal of this fractionated regimen is to eliminate tumor cells while minimizing harm to the surrounding healthy tissues.
- Conclusion: Eliminating cancer stem cells (CSCs) poses significant challenges, as current treatments often fail to target them effectively. Systematic research has yet to provide a reliable method to overcome chemotherapy resistance, limiting our understanding of CSCs' role in tumor heterogeneity. Despite these obstacles, there is optimism that ongoing investigations will eventually lead to effective cancer prevention and treatment strategies.
- Keywords: Cancer stem cells cancer therapy tumor microenvironment (TME)
