Receptor-mediated and enzyme-dependent targeting of cytotoxic anticancer drugs.
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.
Dubowchik
G M
GM
Bristol-Myers Squibb Pharmaceutical Research Institute, Wallingford, CT 06492-7660, USA. dubowchg@bms.com
Walker
M A
MA
D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D002986:Clinical Trials as Topic; D016503:Drug Delivery Systems / Q000379:methods*; D004798:Enzymes / Q000502:physiology*; D006801:Humans; D008081:Liposomes / Q000008:administration & dosage; D009369:Neoplasms / Q000098:blood supply / Q000188:drug therapy* / Q000378:metabolism; D011355:Prodrugs / Q000008:administration & dosage; D011955:Receptors, Drug / Q000502:physiology*
D000911:Antibodies, Monoclonal; D000970:Antineoplastic Agents; D004798:Enzymes; D008081:Liposomes; D011355:Prodrugs; D011955:Receptors, Drug