Antibody鈥揇rug Conjugates and Small Molecule鈥揇rug Conjugates: Opportunities and Challenges for the Development of Selective Anticancer Cytotoxic Agents

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• 作者：Giulio Casi ; Dario Neri
• 刊名：Journal of Medicinal Chemistry
• 出版年：2015
• 出版时间：November 25, 2015
• 年：2015
• 卷：58
• 期：22
• 页码：8751-8761
• 全文大小：528K
• ISSN：1520-4804

文摘

Conventional cancer chemotherapy heavily relies on the use of cytotoxic agents, which typically do not preferentially localize at the tumor site and cause toxicity to normal organs, preventing dose escalation to therapeutically active regimens. In principle, antibodies and other ligands could be used for the selective pharmacodelivery of cytotoxic agents to the neoplastic mass. For many years, the availability of ligands, capable of selective internalization into tumor cells, has been considered to be an essential requirement for the development of targeted cytotoxics. This assumption, however, has recently been challenged on the basis of therapeutic data obtained with noninternalizing drug conjugates. Moreover, quantitative evaluations of the tumor targeting properties of antibodies and of small organic ligands have provided new insights for the implementation of optimal strategies for the development of targeted cytotoxics. In this article, we highlight opportunities and challenges associated with the clinical and industrial development of antibody鈥揹rug conjugates and small molecule鈥揹rug conjugates for cancer therapy.