<!--Definition and medical uses-->
Etoposide, sold under the brand name Vepesid among others, is a chemotherapy medication used for the treatments of a number of types of cancer including testicular cancer, lung cancer, lymphoma, leukemia, neuroblastoma, and ovarian cancer. It is used by mouth or injection into a vein. Use during pregnancy will likely harm the fetus. It is on the World Health Organization's List of Essential Medicines.
Medical uses
Etoposide is used as a form of chemotherapy for cancers such as Kaposi's sarcoma, Ewing's sarcoma, lung cancer, testicular cancer, lymphoma, nonlymphocytic leukemia, and glioblastoma multiforme. It is often given in combination with other drugs (such as bleomycin in treating testicular cancer). It is also sometimes used in a conditioning regimen prior to a bone marrow or blood stem cell transplant.
Pharmacology
Mechanism of action
Etoposide forms a ternary complex with DNA and the topoisomerase II enzyme, which is an enzyme that aids in relaxing negative or positive supercoils in DNA. Topoisomerase II normally will form a double-stranded break in one DNA double-strand, allow another to pass through, and re-ligate the broken strands. Etoposide's binding prevents topoisomerase II from re-ligating the broken DNA strands, which causes the DNA breaks made by topoisomerase II to stay broken, and also prevents the topoisomerase II molecule from leaving the site and relieving tension elsewhere. This results in a double-strand break in the DNA that can have various deleterious effects on the cell, and depletion of topoisomerase II available to relieve further tension. Cancer cells rely on this enzyme more than healthy cells, since they divide more rapidly. Therefore, this causes errors in DNA synthesis and promotes apoptosis of the cancer cell.
Chemistry
thumb|An illustration of the [[mayapple (or "American mandrake"), showing part of the rhizome (at bottom)]]
Etoposide is a semisynthetic derivative of podophyllotoxin from the rhizome of the mayapple (or "American mandrake", Podophyllum peltatum). More specifically, it is a glycoside of podophyllotoxin with a <small>D</small>-glucose derivative. It is chemically similar to the anti-cancer drug teniposide, being distinguished only by a methyl group where teniposide has a thienyl. Both these compounds have been developed with the aim of creating less toxic derivatives of podophyllotoxin.
The substance is a white to yellow-brown, crystalline powder. It is soluble in organic solvents.
The nickname VP-16 likely comes from a compounding of the last name of one of the chemists who performed early work on the drug (von Wartburg) and podophyllotoxin. Another scientist who was integral in the development of podophyllotoxin-based chemotherapeutics was the medical pharmacologist Hartmann F. Stähelin.