The use of chemicals to treat cancer (cancer chemotherapy) started in 1942 with the clinical use of nitrogen mustards by Louis S. Goodman and Alfred Gilman. Subsequent discoveries included mechlorethamine (Mustargen), chlorambucil (1952), and cyclophosphamide (1956). Drugs to block folic acid (also called antimetabolites) were also developed.
Cancer cell division or proliferation leads to the growth of tumours.
Aminopterin (1947) was effective against leukemia, but its adverse effects on white blood cells quickly led to its replacement by methotrexate. In the 1950s, George Hitchings and Charles Heidelberger developed the antimetabolitic mercaptopurine for leukemia and fluorouracil for gastrointestinal and breast tumours.