Prodrug strategies in anticancer chemotherapy

ChemMedChem. 2008 Jan;3(1):20-53. doi: 10.1002/cmdc.200700159.


The majority of clinically approved anticancer drugs are characterized by a narrow therapeutic window that results mainly from a high systemic toxicity of the drugs in combination with an evident lack of tumor selectivity. Besides the development of suitable galenic formulations such as liposomes or micelles, several promising prodrug approaches have been followed in the last decades with the aim of improving chemotherapy. In this review we elucidate the two main concepts that underlie the design of most anticancer prodrugs: drug targeting and controlled release of the drug at the tumor site. Consequently, active and passive targeting using tumor-specific ligands or macromolecular carriers are discussed as well as release strategies that are based on tumor-specific characteristics such as low pH or the expression of tumor-associated enzymes. Furthermore, other strategies such as ADEPT (antibody-directed enzyme prodrug therapy) and the design of self-eliminating structures are introduced. Chemical realization of prodrug approaches is illustrated by drug candidates that have or may have clinical importance.

Publication types

  • Review

MeSH terms

  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacokinetics
  • Clinical Trials as Topic
  • Drug Administration Routes
  • Drug Delivery Systems / methods*
  • Drug Design*
  • Humans
  • Liposomes / administration & dosage
  • Micelles
  • Prodrugs / administration & dosage*
  • Prodrugs / pharmacokinetics
  • Receptors, Cell Surface / metabolism


  • Antineoplastic Agents
  • Liposomes
  • Micelles
  • Prodrugs
  • Receptors, Cell Surface