Cancer Chemotherapy and Pharmacology

, Volume 84, Issue 5, pp 937–958 | Cite as

Prodrugs as drug delivery system in oncology

  • J. Delahousse
  • C. SkarbekEmail author
  • A. Paci
Review Article


The use of conventional chemotherapy in the treatment of cancer has been restricted by the lack of cell specificity, which causes toxicity regarding healthy cells resulting in limiting side effects responsible for low therapeutic efficiency. To overcome these drawbacks, the design of prodrugs has evolved and improved by covalently linking the drug through a degradable spacer. The use of these prodrugs as drug delivery systems, which are able to inactivate the drug during its biodistribution to specifically deliver the drug to its target, is an important breakthrough in cancer therapy. This strategy consisting in the covalent binding of a promoiety to daily used therapeutic compounds has been clinically proven in the design of targeted prodrugs leading enhanced therapeutic efficacy and increase of the therapeutic index. This review summarizes and compares several strategies that improve the therapeutic index of chemotherapy (i.e. conventional drugs) by their chemical transformation into prodrugs improving pharmacokinetic profiles and optimizing administration routes in comparison to the initial drug. This review provides an overview of the methods used to control the structure and function of prodrugs and, ultimately, their current and future potential in increasing the therapeutic index of daily used anticancer drugs. First, prodrugs’ design and their activation within the tumor microenvironment or within the tumor cell will be exposed. Then, the different strategies used leading to these prodrugs will be presented.


Cancer therapy Drug delivery systems Microenvironment Prodrugs Targeting 



This review work was not supported by any grant.

Compliance with ethical standards

Conflict of interest

All authors declare that they have no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.


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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Vectorologie des anticancéreux et des acides nucléiques, UMR 8203, CNRS, Université Paris-Saclay, Gustave Roussy Cancer CampusVillejuifFrance
  2. 2.Service de Pharmacologie, Département de Biologie et Pathologie médicalesGustave Roussy Cancer CampusVillejuifFrance
  3. 3.University Paris-Saclay, Faculté de PharmacieChatenay-MalabryFrance

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