An overview of advancements in screening methods and point-of-care diagnostics for colorectal cancer

Colorectal cancer (CRC) is a significant global health concern, originating from precancerous polyps in the colon or rectum and progressing through genetic and epigenetic alterations. Early-stage CRC is often asymptomatic, underscoring the critical need for effective screening and early detection to improve patient outcomes. This review provides a comprehensive analysis of CRC subtypes, clinical manifestations, diagnostic approaches, and management strategies, with a focus on advancements in point-of-care diagnostics and emerging technologies.

Etiology of CRC
CRC develops through a multistep process involving genetic and epigenetic changes, leading to the transformation of normal epithelial cells into malignant forms. Key pathways include the adenoma-carcinoma sequence, driven by mutations in genes such as APC, KRAS, and p53, and disruptions in signaling pathways like WNT and TGF-β. Molecular subtypes, including microsatellite instability (MSI), chromosomal instability (CIN), and consensus molecular subtypes (CMS), influence tumor behavior, prognosis, and therapeutic response.

Risk Factors
CRC risk factors include modifiable elements such as sedentary lifestyle, tobacco and alcohol use, obesity, and diets high in red or processed meat. Non-modifiable factors include age, family history, inflammatory bowel disease (IBD), and hereditary syndromes like Lynch syndrome and familial adenomatous polyposis (FAP). Gender and racial disparities also play a role, with higher incidence and mortality observed in men and certain ethnic groups. The gut microbiota and chronic inflammation further contribute to CRC pathogenesis.

Point-of-Care Diagnostic Methods
Early detection of CRC relies on a combination of non-invasive and invasive screening methods:

1. Fecal-Based Tests:

   • Fecal Occult Blood Test (FOBT): Detects hidden blood in stool but lacks specificity and requires dietary restrictions.

   • Fecal Immunochemical Test (FIT): Targets human globin, offering higher sensitivity and specificity without dietary constraints.

   • Fecal DNA Tests: Identify genetic mutations and methylation markers (e.g., KRAS, BMP3) associated with CRC, though they may yield false positives.

2. Blood-Based Tests:

   • Septin9 Assay: Detects methylated DNA but has low sensitivity for adenomas.

   • Liquid Biopsy: Analyzes circulating tumor DNA (ctDNA) for real-time monitoring but is not yet a standalone diagnostic tool.

3. Endoscopic Techniques:

   • Colonoscopy: The gold standard for CRC screening, allowing direct visualization, biopsy, and polyp removal. Limitations include invasiveness and need for bowel preparation.

   • Sigmoidoscopy: Examines the distal colon and rectum but misses proximal lesions.

   • Capsule Endoscopy: A non-invasive alternative for patients unable to tolerate colonoscopy.

4. Radiological Methods:

   • CT Colonography: Provides 3D colon images but requires bowel preparation and may miss small polyps.

   • Barium Enema: Rarely used due to low sensitivity compared to modern techniques.

Integration of Advanced Technologies
Recent advancements enhance CRC diagnostics:

• Single-Cell Sequencing (SCS): Reveals tumor heterogeneity and identifies driver mutations.

• Spatial Transcriptomics (ST): Maps gene expression within tissue architecture, aiding in subtype stratification.

• Artificial Intelligence (AI): Improves polyp detection during colonoscopy, automates histopathological analysis, and integrates multi-omics data for personalized risk prediction.

Lifestyle Management
Modifiable risk factors can be addressed through dietary changes (high fiber, low red meat), physical activity, and avoidance of tobacco and excessive alcohol. Chemopreventive strategies, including natural compounds and prebiotics, show promise in reducing CRC risk.

Limitations and Future Perspectives
Current screening methods face challenges such as variable adherence, accessibility, and limitations in detecting early-stage lesions. Future efforts should focus on developing uniform global guidelines, leveraging emerging technologies for precision medicine, and promoting public health initiatives to reduce CRC incidence through lifestyle interventions.

Conclusions
CRC remains a leading cause of cancer-related mortality, but advancements in screening and diagnostics offer hope for early detection and improved outcomes. A multifaceted approach combining innovative technologies, personalized strategies, and lifestyle modifications is essential to reduce the global burden of CRC.

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The study was recently published in the Cancer Screening and Prevention.

Cancer Screening and Prevention (CSP) publishes high-quality research and review articles related to cancer screening and prevention. It aims to provide a platform for studies that develop innovative and creative strategies and precise models for screening, early detection, and prevention of various cancers. Studies on the integration of precision cancer prevention multiomics where cancer screening, early detection and prevention regimens can precisely reflect the risk of cancer from dissected genomic and environmental parameters are particularly welcome.

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