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

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.