Antibodies vs. aptamers in cancer diagnosis and therapy: a comparative analysis of clinical applications, mechanisms, and future directions.

Abstract

Cancer remains a leading cause of morbidity and mortality worldwide, necessitating the continued development of precision therapies that can selectively target tumor cells while minimizing off-target toxicity. Among emerging biotherapeutic strategies, monoclonal antibodies and nucleic acid aptamers (DNA and RNA) have gained prominence for their specificity and versatility in targeted cancer therapy. Antibodies are Y-shaped immunoglobulin proteins capable of recognizing tumor-associated antigens, playing a pivotal role not only in therapy but also in cancer diagnosis and detection by targeting specific tumor markers, supporting imaging modalities, and enabling immunohistochemistry; they are also the foundation of multiple approved antibody-drug conjugates. Aptamers, by contrast, are short, single-stranded DNA or RNA oligonucleotides that fold into three-dimensional structures capable of high-affinity target binding, offering advantages such as smaller molecular size, lower immunogenicity, and facile chemical synthesis. This narrative review is guided by the central question: How do antibodies and aptamers compare as platforms for targeted cancer diagnostics and therapeutics? To address this, we systematically applied the PRISMA framework to a comprehensive literature search conducted using PubMed, Scopus, and Web of Science, ensuring the systematic selection and evaluation of relevant studies published up to April 2025. Our review highlights the strengths and limitations of each biotherapeutic approach. Antibodies offer established clinical efficacy, immune effector function via Fc-mediated interactions, and favorable pharmacokinetics, but face challenges related to tumor penetration, immunogenicity, and manufacturing complexity. Aptamers, while still largely in preclinical stages, show promise due to enhanced tumor infiltration, rapid renal clearance, and engineering flexibility, though their in vivo stability and immunogenicity require further optimization. In conclusion, this review contributes a structured comparison of two major biotherapeutic platforms, emphasizing their roles not only in therapy but also in diagnosis. Both platforms hold significant clinical promise in diagnosis and therapeutics. Future research should focus on overcoming resistance mechanisms, enhancing delivery systems, and evaluating combination strategies that harness the complementary strengths of antibodies and aptamers.

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