Aptamer-Drug Conjugates (ApDCs): Transformative approaches in targeted cancer therapy and precision oncology

Aptamers are emerging as highly promising tools for targeted cancer therapy, offering superior specificity and affinity over traditional approaches. This review comprehensively explores the cutting-edge landscape of aptamer-drug conjugates (ApDCs) for precision oncology, highlighting their innovative design and therapeutic potential. We explore how breakthroughs in SELEX technology and bioinformatics are revolutionizing aptamer discovery against cancer biomarkers, enabling the creation of highly effective ApDCs. The article systematically examines diverse conjugation strategies-from covalent linkages to nanoparticle-based delivery-and their crucial role in enhancing drug delivery to tumors. We showcase compelling preclinical successes of ApDCs, such as aptamer-gemcitabine and aptamer-doxorubicin conjugates, which demonstrate potent, tumor-selective cytotoxicity with minimal off-target effects. Despite these advancements, challenges in clinical translation, including stability, immunogenicity, and scalable production, persist. This review discusses promising solutions like multivalent aptamers and bispecific constructs, and provides insights from FDA-approved aptamer therapeutics and those in clinical trials. By critically assessing current limitations and future directions, this review underscores the transformative potential of aptamer engineering and novel conjugation strategies in reshaping targeted cancer therapy and personalized medicine.