Towards antibody-drug conjugates and prodrug strategies with extracellular stimuli-responsive drug delivery in the tumor microenvironment for cancer therapy.

Abstract

The design of innovative anticancer chemotherapies with superior antitumor efficacy and reduced toxicity continues to be a challenging endeavor. Recently, the success of Adcetris® and Kadcyla® made antibody-drug conjugates (ADCs) serious contenders to reach the envied status of Paul Ehrlich's "magic bullet". However, ADCs classically target overexpressed and internalizing antigens at the surface of cancer cells, and in solid tumors are associated with poor tumor penetration, insufficient targeting in heterogeneous tumors, and appearance of several resistance mechanisms. In this context, alternative non-internalizing ADCs and prodrugs have been developed to circumvent these limitations, in which the drug can be selectively released by an extracellular stimulus in the tumor microenvironment. Each strategy and method of activation will be discussed as potential alternatives to internalizing ADCs for cancer therapy.

• Authors: Nicolas Joubert, Caroline Denevault-Sabourin, Francesca Bryden, Marie-Claude Viaud-Massuard
• Journal: European journal of medicinal chemistry (Eur J Med Chem) Vol. 142 Pg. 393-415 (Dec 15 2017) ISSN: 1768-3254 [Electronic] France
• PMID: 28911823 (Publication Type: Journal Article, Review)
• Copyright: Copyright © 2017 Elsevier Masson SAS. All rights reserved.

Chemical References

• Antineoplastic Agents, Immunological
• Immunoconjugates
• Prodrugs

Topics

• Animals
• Antineoplastic Agents, Immunological (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Drug Delivery Systems
• Drug Discovery
• Humans
• Immunoconjugates (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Neoplasms (drug therapy)
• Prodrugs (administration & dosage, pharmacokinetics, pharmacology, therapeutic use)
• Tumor Microenvironment (drug effects)