Abstract
Colorectal cancer (CRC) continues to represent a substantial worldwide health burden. Accurate risk classification and early detection have a significant impact on prognosis. There is still a significant percentage of patients who are diagnosed at advanced stages, notwithstanding the progress that has been made in screening and treatment. Thus, improved molecular tools that encompass the biological complexity of CRC are needed. High-throughput technologies have expanded the biomarker array for CRC screening, prognosis, and therapeutic prediction. This review summarizes evidence on established and emerging molecular tools from tumor tissue, blood, and stool samples, such as DNA mutations, methylation markers, RNA signatures, circulating tumor DNA (ctDNA), circulating cell-free DNA (cfDNA), extracellular vesicles, and multi-omic composite assays. These provide alternatives to conventional approaches that are relatively less invasive and more sensitive. Prognostic biomarkers-such as RAS, BRAF, HER2 alterations, mismatch repair deficiency, tumor mutational burden, methylation signatures, and non-coding RNAs-provide insight into tumor behavior and recurrence risk. To guide targeted therapies, immunotherapies, and chemotherapy response, predictive biomarkers such as RAS/BRAF mutations, HER2 amplification, MSI-H/dMMR status, POLE/POLD1 mutations, DNA methylation panels, miRNAs, lncRNAs, and liquid biopsy markers are crucial. Emerging technologies such as multi-omics, AI-enhanced biomarker discovery, and novel liquid biopsy components (evDNA, circRNAs) pave the way to precision oncology. These molecular tools have the potential to change how CRC is managed by earlier detection and more precise predictive biomarkers. However, large-scale validation and clinical standardization are still crucial for their extensive utilization.