Drug conjugate-based anticancer therapy - Current status and perspectives

• Published in: Cancer letters 2023-01, Vol.552, p.215969, Article 215969
• Main Authors: Yang, Yuqi, Wang, Shuhang, Ma, Peiwen, Jiang, Yale, Cheng, Keman, Yu, Yue, Jiang, Ning, Miao, Huilei, Tang, Qiyu, Liu, Funan, Zha, Yan, Li, Ning
• Format: Article
• Language: English
• Subjects: Amino acids; Antibodies; Antibody; Antigens; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Cancer therapies; Clinical trials; Cytotoxic agents; Cytotoxicity; Design; Drug conjugate; Drug Delivery Systems; Drug development; Enzymes; FDA approval; Humans; Immunoconjugates - pharmacology; Immunoconjugates - therapeutic use; Linker; Molecular weight; Neoplasms - drug therapy; Payload; Peptide; Peptides; Pharmaceutical Preparations; Polymer; Toxicity; Tumors
• ISSN: 0304-3835; 1872-7980
• DOI: 10.1016/j.canlet.2022.215969

Drug conjugates are conjugates comprising a tumor-homing carrier tethered to a cytotoxic agent via a linker that are designed to deliver an ultra-toxic payload directly to the target cancer cells. This strategy has been successfully used to increase the therapeutic efficacy of cytotoxic agents and reduce their toxic side effects. Drug conjugates are being developed worldwide, with the potential to revolutionize current cancer treatment strategies. Antibody-drug conjugates (ADCs) have developed rapidly, and 14 of them have received market approval since the first approval event by the Food and Drug Administration in 2000. However, there are some limitations in the use of antibodies as carriers. Other classes of drug conjugates are emerging, such as targeted drugs conjugated with peptides (peptide-drug conjugates, PDCs) and polymers (polymer-drug conjugates, PolyDCs) with the remaining constructs similar to those of ADCs. These novel drug conjugates are gaining attention because they overcome the limitations of ADCs. This review summarizes the current state and advancements in knowledge regarding the design, constructs, and clinical efficacy of different drug conjugates. •Drug conjugates (DC) increase the therapeutic efficacy of cytotoxic agents.•Main DC involve antibodies, peptides and polypeptides as carriers.•Peptides and polypeptides are gaining attention for their simpler design.•Limitations exist in all types of DC but diverse strategies are being developed.