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Clinical application of CTCs as a therapeutic-guiding marker for stage II CRC patients re- ceiving adjuvant chemotherapy.
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The ability to predict or detect colorectal cancer (CRC) recurrence early after surgery enables physicians to apply appropriate treatment plans and different follow-up strategies to improve patient survival. Overall, 30–50% of CRC patients experience cancer recurrence after radical surgery, but current surveillance tools have limitations in the pre...
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Context 1
... described above, CTCs are a potential prognostic factor for evaluating nonmetastatic (stage I-III) CRC recurrence, but studies analyzing their utility in only stage II CRC patients are limited (Table 2). For instance, Koch et al. conducted a pilot study to analyze the presence of CTCs by RT-PCR in stage II CRC and its correlation with survival [58]. ...Context 2
... the presence of CTCs indicates a worse prognosis in patients with stage II CRC, some studies have investigated the potential of CTCs as a therapeutic marker in patients with stage II CRC (Table 2). Recently, one study demonstrated that the use of CTCs could guide the choice of adjuvant chemotherapy [81]. ...Citations
... ECM proteins, such as fibronectin and collagen, present on the endothelial surface, promote CTC adhesion via integrins, initiating their exit from circulation. After adhering, CTCs employ ECM-remodeling enzymes, including heparinase [66,67] and MMPs [68], to degrade the endothelial basement membrane [69], allowing them to infiltrate the underlying tissue and establish new colonies. The ECM's role in metastasis underscores the intricate relationship between cancer cells and their surrounding microenvironment. ...
The liver is the most common site of metastasis of colorectal cancer (CRC), and colorectal liver metastasis is one of the major causes of CRC-related deaths worldwide. The tumor microenvironment, particularly the extracellular matrix (ECM), plays a critical role in CRC metastasis and chemoresistance. Based on findings from clinical and basic research, this review attempts to offer a complete understanding of the role of the ECM in colorectal liver metastasis and to suggest potential ways for therapeutic intervention. First, the ECMs’ role in regulating cancer cell fate is explored. We then discuss the hepatic ECM fingerprint and its influence on the metastatic behavior of CRC cells, highlighting key molecular interactions that promote metastasis. In addition, we examine how changes in the ECM within the metastatic niche contribute to chemoresistance, focusing on ECM remodeling by ECM stiffening and the activation of specific signaling pathways. Understanding these mechanisms is crucial for the development of novel strategies to overcome metastasis and improve outcomes for CRC patients.
... Similarly, CTCs are a safe and minimally invasive alternative to radiological scans and colonoscopies, offering real-time monitoring of cancer efficacy and recurrence. Despite these advantages, technical limitations still impede its broader clinical application (112). Tumor tissue-or serum-based proteomics can generate large amounts of valuable data for predicting response to nCRT in patients with LARC. ...
Neoadjuvant chemoradiotherapy (nCRT) followed by total mesorectal excision (TME) and selective use of adjuvant chemotherapy is currently considered the standard of care for locally advanced rectal cancer (LARC). Despite this, the concept of organ preservation is gradually challenging this approach. The management of complete clinical remission (cCR) lacks international consensus, leading scholars to develop their own perspectives based on well-designed studies and long-term data from large multicenter cohorts. To ensure appropriate treatment, this review focuses on the choice of neoadjuvant therapy, criteria for defining cCR, and treatment strategies for patients who achieve cCR after neoadjuvant therapy. By providing guidance on the accurate management of LARC patients after cCR, this review aims to prevent over- or under-treatment.
... While CTCs are whole tumor cells captured in the bloodstream, ctDNA consists of fragments of DNA shed by apoptotic tumor-derived cells. ctDNA may serve as a precise tool for monitoring cancer relapse during CRC follow-up [30]. ...
Carcinoembryonic antigen(CEA) is a routine marker employed for follow-up of colorectal tumors. We aimed to determine whether a CEA increase within the normal range can be linked to a risk of recurrence. From the period of 2006–2013 we selected 78 consecutive patients with colorectal cancer, who underwent curative surgery with or without neo-/adjuvant chemo- or radiotherapy and had proper follow-up procedures. For analyzing CEA fluctuation, we used the smallest value of the CEA during follow-up as the reference. With the aid of a Chi-squared test, we have chosen the value of 1.1 ng/mL for significant CEA fluctuation. A total of 43.6% of patients had fluctuations in CEA of at least 1.1 ng/mL, with or without increases above 5 ng/mL. From these, in 79.4% of patients, the increases in CEA were explained either by recurrence (44.1%), adjuvant chemotherapy (20.6%) or benign pathology (14.7%). In 23% of the recurrences, a CEA increase of at least 1.1 ng/mL, but below 5 ng/mL, preceded the clinical relapse by a median of 8 months. Our conclusion is that an increase in CEA levels by at least 1.1 ng/mL within the normal range after curative treatment for colorectal cancer may serve as an early indicator of relapse or could be associated with other pathological conditions.
Investigating the molecular and genetic characteristics of circulating tumor cells (CTCs) presents a promising approach for personalizing treatment in patients with malignant neoplasms, given the limitations of traditional biopsy and histopathology. This study aimed to isolate, characterize, and analyze CTC dynamics in the peripheral blood of 30 patients with metastatic lung cancer to develop criteria for treatment response and prognosis. We detected CTCs before the start of the treatment and monitored changes during treatment, correlating these with responses evaluated by standard imaging methods. A decrease in the CTCs in the course of the therapy was linked to a favorable tumor response, while the stable CTC counts indicated a lack of response and poor survival prognosis. The OS of patients was analyzed and compared with the initial number of CTCs in peripheral blood samples. The significant reductions in median OS were evident in patients with >3 total CTCs at baseline compared to those with ≤3 total CTCs (median survival 26 months, n = 10, vs. median survival 8 months, n = 19, respectively with HR = 2.6, 95% CI 1.07 to 6.4).
Colorectal cancer (CRC) is the third most common cancer and a leading cause of cancer-related mortality worldwide, with prognosis significantly deteriorating at advanced stages. While current diagnostic methods, such as colonoscopy and tissue biopsy, are widely employed in clinical practice, they are invasive, expensive, and limited in assessing tumor heterogeneity and monitoring disease processes, including therapy response. Therefore, early and accurate detection, coupled with minimal invasion and cost-effective strategies, are critical for improving patient outcomes. Liquid biopsy has emerged as a promising, minimally invasive alternative, enabling the detection of tumor-derived components. This approach is increasingly utilized in clinical settings. The current key liquid biopsy modalities in CRC include circulating tumor DNA (ctDNA), circulating tumor cells (CTCs), and RNA-based biomarkers such as long non-coding RNAs (lncRNAs), microRNAs(miRNAs), and circular RNAs (circRNAs), and tumor-educated platelets (TEPs). These methods provide valuable insights into genetic and epigenetic tumor alterations, and serve as indicators for early detection, treatment monitoring, and recurrence prediction. However, challenges such as assay standardization and variability in sensitivity persist. This review delves into the clinical applications of liquid biopsy in CRC management, highlighting the transformative roles of ctDNA, CTCs, and non-coding RNAs, TEPs in early detection, prognostic assessment, and personalized therapy. In addition, it addresses current limitations and explores potential advancements to facilitate their integration into routine clinical practice.
Circulating tumor cells (CTCs) are cancer cells that shed from the primary tumor and enter into body fluids of the patient, where they travel to distant sites and ultimately form metastasis. Understanding the biology of CTCs, in particular at the critical stages of their itinerary, holds promises for better cancer cure. Since the beginning of this century, liquid biopsy has steadily grown to be a keen area of research due to its non-invasive features. As one of the most promising tumor biomarkers, CTCs have shown great potential in cancer diagnosis, prognosis, treatment response monitoring, and the exploration of biological mechanisms. Although various types of isolation and detection technologies emerge constantly, the rarity and heterogeneity of CTCs still pose huge challenges for these methods and make them inefficient. In addition, the clinical practice of different technologies still lacks reasonable and uniform standards. In this review, we provide a detailed overview of the isolation and enrichment strategies of CTCs, as well as their advantages and limitations. By summarizing the current status and suggesting future areas of CTCs research, we hope to continue the concerted effort for pushing forward the clinical application of CTCs, which may represent a paradigm shift for cancer theranostics in the future.
Colorectal cancer (CRC) continues to be a global health concern, necessitating further research into its complex
biology and innovative treatment approaches. The etiology, pathogenesis, diagnosis, and treatment of colorectal
cancer are summarized in this thorough review along with recent developments. The multifactorial nature of
colorectal cancer is examined, including genetic predispositions, environmental factors, and lifestyle decisions.
The focus is on deciphering the complex interactions between signaling pathways such as Wnt/β-catenin, MAPK,
TGF-β as well as PI3K/AKT that participate in the onset, growth, and metastasis of CRC. There is a discussion of
various diagnostic modalities that span from traditional colonoscopy to sophisticated molecular techniques like
liquid biopsy and radiomics, emphasizing their functions in early identification, prognostication, and treatment
stratification. The potential of artificial intelligence as well as machine learning algorithms in improving accuracy
as well as efficiency in colorectal cancer diagnosis and management is also explored. Regarding therapy, the
review provides a thorough overview of well-known treatments like radiation, chemotherapy, and surgery as
well as delves into the newly-emerging areas of targeted therapies as well as immunotherapies. Immune
checkpoint inhibitors as well as other molecularly targeted treatments, such as anti-epidermal growth factor
receptor (anti-EGFR) as well as anti-vascular endothelial growth factor (anti-VEGF) monoclonal antibodies, show
promise in improving the prognosis of colorectal cancer patients, in particular, those suffering from metastatic
disease. This review focuses on giving readers a thorough understanding of colorectal cancer by considering its
complexities, the present status of treatment, and potential future paths for therapeutic interventions. Through
unraveling the intricate web of this disease, we can develop a more tailored and effective approach to treating
CRC.
