Etoposide: four decades of development of a topoisomerase II inhibitor.
Podophyllin-containing materials have been used as folk medicines for centuries. In the 1950s, scientists began a search to identify a more effective podophyllotoxin derivative. These efforts eventually resulted in the development of a new class of antineoplastic agents which target the DNA unwinding enzyme, topoisomerase II. The history of the development of one of the first identified topoisomerase II inhibitors, etoposide, is reviewed in this paper. Critical developments in etoposide's mechanism of action, pharmacology and administration schedule are summarised. The clinical benefits of the recently marketed etoposide prodrug, etoposide phosphate (Etopophos) are also detailed. The current status of other clinically approved anticancer agents which target topoisomerase II is briefly reviewed.
Hande
K R
KR
Vanderbilt University School of Medicine, Department of Medical Oncology, Nashville VA Medical Center, USA.
D000284:Administration, Oral; D018943:Anthracyclines / Q000627:therapeutic use; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use*; D005047:Etoposide / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D008942:Mitoxantrone / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy* / Q000201:enzymology; D013678:Technology, Pharmaceutical / Q000639:trends; D013713:Teniposide / Q000627:therapeutic use; D059005:Topoisomerase II Inhibitors
D018943:Anthracyclines; D000972:Antineoplastic Agents, Phytogenic; D059005:Topoisomerase II Inhibitors; D005047:Etoposide; D013713:Teniposide; D008942:Mitoxantrone