Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs

Pharmacol Ther. 1999 Aug;83(2):67-123. doi: 10.1016/s0163-7258(99)00018-2.

Abstract

This review is a survey of various approaches to targeting cytotoxic anticancer drugs to tumors primarily through biomolecules expressed by cancer cells or associated vasculature and stroma. These include monoclonal antibody immunoconjugates; enzyme prodrug therapies, such as antibody-directed enzyme prodrug therapy, gene-directed enzyme prodrug therapy, and bacterial-directed enzyme prodrug therapy; and metabolism-based therapies that seek to exploit increased tumor expression of, e.g., proteases, low-density lipoprotein receptors, hormones, and adhesion molecules. Following a discussion of factors that positively and negatively affect drug delivery to solid tumors, we concentrate on a mechanistic understanding of selective drug release or generation at the tumor site.

Publication types

  • Review

MeSH terms

  • Antibodies, Monoclonal / administration & dosage
  • Antineoplastic Agents / administration & dosage*
  • Clinical Trials as Topic
  • Drug Delivery Systems / methods*
  • Enzymes / physiology*
  • Humans
  • Liposomes / administration & dosage
  • Neoplasms / blood supply
  • Neoplasms / drug therapy*
  • Neoplasms / metabolism
  • Prodrugs / administration & dosage
  • Receptors, Drug / physiology*

Substances

  • Antibodies, Monoclonal
  • Antineoplastic Agents
  • Enzymes
  • Liposomes
  • Prodrugs
  • Receptors, Drug