Protein-targeted aptamers in liquid biopsy: from efficient screening to precise cancer diagnosis

Early and precise cancer diagnosis is a substantial way to improve patient survival. However, the heterogeneity of cancer and the challenges associated with sampling tissues from concealed anatomical sites hinder reliable diagnosis using conventional clinical approaches. In this case, by leveraging noninvasive sampling and real-time molecular analysis, liquid biopsy offers new opportunities for individualized cancer diagnostics. Although circulating tumor cells (CTCs) and extracellular vesicles (EVs) carry key molecular information, the effective isolation and detection of these rare circulating biomarkers remain technically demanding. Aptamers, which are initially produced by an <i>in vitro</i>-optimized process termed systematic evolution of ligands by exponential enrichment (SELEX), refer to a special category of single-stranded functional oligonucleotides for the specific recognition of targets by folding into unique tertiary structures. Benefiting from their flexible design, chemical/thermal stability, and convenience in modification compared with conventional antibodies, aptamers are widely applied in liquid biopsy for accurate cancer diagnosis in molecular medicine. In this review, we present the emerging methods for detecting biomarkers of liquid biopsy based on aptamers, which are screened by various methods of protein-targeting SELEX technologies. By reviewing the researh progress of aptamers in cancer-associated liquid biopsy, we present our vision on the promising application of aptamers in accurate cancer diagnosis.