Unveiling Aptamers for Targeted Tumour Therapies and Detection: Systematic Evolution of Ligands by Exponential...

Aptamers are short single-stranded DNA (ssDNA) or RNA (ssRNA) molecules that bind cancer-associated targets with high specificity and low immunogenicity. Their small size and structural flexibility make them an attractive alternative to antibodies for diagnosing and treating cancer. The way in which the aptamer Selection Method (SELEX) is performed plays a key role in determining whether aptamers will be successful in oncology. The way the selection strategy mimics the tumour's biological environment and the clinical intent behind the selection of the aptamer determine the likelihood of finding useful aptamers using the SELEX technique. This review discusses how various SELEX formats have been used in cancer research, including protein, cell, tissue, serum, magnetic bead, microfluidic, in vivo, and hybrid-based SELEX approaches. These formats are examined as separate methods, with a focus on comparing and evaluating their efficacy against a wide range of cancer targets and biological environments. Examples of studies utilising SELEX-derived aptamers in diagnostic imaging, histopathology, and targeted drug delivery are provided. Roadblocks to drug development, including the decreasing biological relevance of models, potential selection bias, and tumor variability, are also discussed. In addition, areas in which emerging technologies-such as patient-derived selection systems, advances in microfluidic processes, and the maximum achievable resolution of single-cell experiments- can improve the environment for drug selection and development are highlighted. The authors provide a framework for applying SELEX as a context-based selection tool for developers, enabling the development of equally effective clinical trial designs that are more aligned with precision oncology.