Cancer Genetics and Epigenetics 2024, Vol.12, No.5, 254-269 http://medscipublisher.com/index.php/cge 256 CTCs and ctDNA offer several advantages over traditional diagnostic methods. They provide real-time information about tumor dynamics, can detect minimal residual disease, and help monitor treatment response and disease progression. However, challenges remain in standardizing detection methods and improving sensitivity and specificity (Kantara et al., 2014; Shahjehan et al., 2019; Sundling and Lowe, 2019; Alese et al., 2022). 2.3 The need for non-invasive diagnostic approaches The traditional methods for diagnosing colon cancer, such as colonoscopy and biopsy, are invasive and often uncomfortable for patients. These procedures also carry risks such as bleeding and perforation. As a result, there is a significant need for non-invasive diagnostic approaches that can accurately detect colon cancer at an early stage, monitor disease progression, and predict relapse (Marcuello et al., 2019; Chelakkot et al., 2020). CTCs have shown potential as prognostic markers in colon cancer. Studies have demonstrated that the presence of CTCs in the blood is associated with poor survival and increased risk of metastasis. For instance, higher baseline levels of CTCs have been linked to worse outcomes in patients with metastatic colon cancer (Kantara et al., 2014; Sundling and Lowe, 2019; Chelakkot et al., 2020). Additionally, the detection of CTCs after surgery or chemotherapy can indicate minimal residual disease and predict recurrence, providing valuable information for tailoring adjuvant therapy (Tie et al., 2014; Tie et al., 2016). Similarly, ctDNA analysis has proven to be a valuable tool for detecting minimal residual disease and predicting relapse in colon cancer patients. Research has shown that ctDNA can identify relevant genetic mutations and provide insights into tumor heterogeneity. For example, the presence of ctDNA after surgery has been associated with a higher risk of recurrence, suggesting that these patients may benefit from additional therapeutic interventions (Tie et al., 2014; Tie et al., 2016; Shahjehan et al., 2019). 3 Circulating Tumor Cells (CTCs): An Introduction Circulating tumor cells (CTCs) are cancer cells that have detached from the primary tumor and entered the bloodstream. These cells are considered to be the precursors of metastasis, which is the spread of cancer to distant organs. The detection and analysis of CTCs offer a non-invasive method to monitor cancer progression and response to treatment, often referred to as a "liquid biopsy" (Sundling and Lowe, 2019; Yang et al., 2019; Zhang et al., 2020). The clinical utility of CTCs has been explored in various cancers, including colorectal cancer, where they serve as prognostic and predictive biomarkers (Cabel et al., 2017; Chelakkot et al., 2022; Ring et al.,2023). 3.1 Definition and characteristics of CTCs Circulating tumor cells (CTCs) are defined as cancer cells that have shed from the primary tumor or metastatic sites into the bloodstream. These cells can be found as single cells or clusters and are considered rare events in the blood circulation (Pantel and Speicher, 2016; Sundling and Lowe, 2019). CTCs are characterized by their ability to survive in the bloodstream, evade immune detection, and potentially colonize distant organs to form metastases (Masuda et al., 2016; Liu et al., 2021). CTCs exhibit various phenotypic and genotypic characteristics that can be used for their identification and isolation. Common markers include epithelial cell adhesion molecule (EpCAM), cytokeratins (CKs), and other tumor-specific antigens (Masuda et al., 2016; Yang et al., 2019). Advances in detection technologies, such as immunocytochemistry and next-generation sequencing, have improved the sensitivity and specificity of CTC identification (Masuda et al., 2016; Cabel et al., 2017). 3.2 Biological significance of CTCs in cancer The biological significance of CTCs lies in their role in the metastatic cascade. Metastasis is a complex process involving the detachment of cancer cells from the primary tumor, intravasation into the bloodstream, survival in circulation, extravasation into distant tissues, and colonization to form secondary tumors (Fig.1.b) (Masuda et al., 2016; Pantel and Speicher, 2016). CTCs are considered key players in this process, and their presence in the bloodstream is often associated with poor prognosis and advanced disease stages (Gazzaniga et al., 2012; ; Cristofanilli et al., 2019). During dissemination in the bloodstream, CTCs interact with various hematopoietic
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