Antibody–Drug Conjugates and Peptide–Drug Conjugates: Current Understandings and Future Perspectives

ABSTRACT

Antibody–drug conjugates (ADCs) and peptide–drug conjugates (PDCs) are modular targeted therapeutics in which molecular recognition is coupled with controlled payload delivery. Owing to their high specificity and precision, they have been regarded as a transformative paradigm for cancer therapy. In this review, current understandings and future perspectives of ADCs and PDCs are synthesized across rational design principles, historical evolution, clinical translation, and emerging formats, aiming to improve practical comprehension and application in oncology. Key determinants of performance: target selection, antibody or peptide carrier attributes, linker stability and cleavage mechanisms, payload classes, and conjugation strategies, are additionally discussed. Milestone advances achieved spanning hematologic malignancies and solid tumors are emphatically summarized to provide a framework by which future conjugate development may be contextualized. In parallel, the expansion of PDCs as complementary platforms is outlined, and advantages are highlighted, while limitations are also considered. ADCs and PDCs still face challenges such as toxicity, resistance, and poor stability. However, through breakthroughs including linker optimization, novel payloads, bispecific designs, and AI‐driven approaches, future conjugated drugs will continue to evolve toward personalization, combination therapies, and broader indications. This article provides a systematic synthesis of extant research, thereby facilitating the future advancement of targeted conjugate drugs toward greater precision and individualization. It holds significant academic value as a reference resource and offers practical guidance for the development of novel antineoplastic therapeutics.