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Prodrug Applications for Targeted Cancer Therapy

  • Review Article
  • Theme: Chemical, Pharmacologic, and Clinical Perspectives of Prodrugs
  • Published:
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Abstract

Prodrugs are widely used in the targeted delivery of cytotoxic compounds to cancer cells. To date, targeted prodrugs for cancer therapy have achieved great diversity in terms of target selection, activation chemistry, as well as size and physicochemical nature of the prodrug. Macromolecular prodrugs such as antibody-drug conjugates, targeted polymer-drug conjugates and other conjugates that self-assemble to form liposomal and micellar nanoparticles currently represent a major trend in prodrug development for cancer therapy. In this review, we explore a unified view of cancer-targeted prodrugs and highlight several examples from recombinant technology that exemplify the prodrug concept but are not identified as such. Recombinant “prodrugs” such as engineered anthrax toxin show promise in biological specificity through the conditionally targeting of multiple cellular markers. Conditional targeting is achieved by structural complementation, the spontaneous assembly of engineered inactive subunits or fragments to reconstitute functional activity. These complementing systems can be readily adapted to achieve conditionally bispecific targeting of enzymes that are used to activate low-molecular weight prodrugs. By leveraging strengths from medicinal chemistry, polymer science, and recombinant technology, prodrugs are poised to remain a core component of highly focused and tailored strategies aimed at conditionally attacking complex molecular phenotypes in clinically relevant cancer.

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ACKNOWLEDGMENTS

G.M.K.P. received financial support from Grant Number UL1RR025014 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH) and NIH Roadmap for Medical Research, and the College of Pharmacy, Washington State University.

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  1. Erin L. Boland

    Present address: Department of Structural & Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, 70112, USA

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, College of Pharmacy, Washington State University, P.O. Box 1495, Spokane, Washington, 99210-1495, USA

    Irene Giang, Erin L. Boland & Gregory M. K. Poon

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  1. Irene Giang
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  2. Erin L. Boland
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  3. Gregory M. K. Poon
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Correspondence to Gregory M. K. Poon.

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Giang, I., Boland, E.L. & Poon, G.M.K. Prodrug Applications for Targeted Cancer Therapy. AAPS J 16, 899–913 (2014). https://doi.org/10.1208/s12248-014-9638-z

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