Aptamer-Based Strategies for Colorectal Cancer Detection: Emerging Technologies and Future Directions.

Colorectal cancer (CRC) remains a leading cause of cancer-related morbidity and mortality worldwide, with patient outcomes highly dependent on early and accurate diagnosis. However, existing diagnostic methods, such as colonoscopy, fecal occult blood testing, and imaging, are often invasive, costly, or lack sufficient sensitivity and specificity, particularly in early-stage disease. In this context, aptamers, which are synthetic single-stranded oligonucleotides capable of binding to specific targets with high affinity, have emerged as a powerful alternative to antibodies for biosensing applications. This review provides a comprehensive overview of aptamer-based strategies for CRC detection, spanning from biomarker discovery to clinical translation. We first examine established and emerging CRC biomarkers, including those approved by regulatory agencies, described in patents, and shared across multiple cancer types. We then discuss recent advances in aptamer selection and design, with a focus on SELEX variants and in silico optimization approaches tailored to CRC-relevant targets. The integration of aptamers into cutting-edge sensing platforms, such as electrochemical, optical, and nanomaterial-enhanced aptasensors, is highlighted, with emphasis on recent innovations that enhance sensitivity, portability, and multiplexing capabilities. Furthermore, we explore the convergence of aptasensing with microfluidics, and wearable technologies to enable intelligent, miniaturized diagnostic systems. Finally, we consider the clinical and regulatory pathways for point-of-care implementation, as well as current challenges and opportunities for advancing the field. By outlining the technological and translational trajectory of aptamer-based CRC diagnostics, this review aims to provide a roadmap for future research and interdisciplinary collaboration in precision oncology.