Cancer Chemotherapy 1946 – A Revolution in Cancer Treatment

Many cancer chemotherapies act by inhibiting rapid division, a characteristic feature of cancer cells. Unfortunately, chemotherapy drugs also destroy rapidly dividing healthy cells, such as those in hair follicles, the digestive tract and bone marrow. 

Surprisingly, one of the first effective anticancer drugs was discovered by American pharmacologists Alfred Gilman and Louis Goodman through secret wartime research. Studies of thousands of people accidentally exposed to American-made mustard gas bombs showed that this chemical warfare agent damaged rapidly growing white blood cells. Scientists thought this might be useful in treating certain lymphomas (cancers of particular white blood cells). In 1943, when a related nitrogen compound was injected into a person with non-Hodgkin lymphoma, Gilman and Goodman observed a dramatic but temporary reduction in tumour masses. The government allowed the findings to be published in 1946.

• In 1948, American pathologist Sidney Farber discovered that a drug called methotrexate, which blocks the action of enzymes requiring the vitamin folate, induced remission in children with acute lymphoblastic leukaemia. 
• In 1951, chemists synthesised a drug called 6-mercaptopurine (6-MP), which inhibits DNA synthesis and is useful in treating childhood leukaemia. 
• In 1956, methotrexate was used effectively to treat a solid tumour called choriosarcoma in a woman. 
• In 1965, combinations of different anticancer drugs were found to be beneficial. 
• In 1969, platinum-based drugs that cause DNA cross-linking were reported to trigger programmed cell death (apoptosis).

There are several main categories of chemotherapy drugs that affect cell division or DNA synthesis: 

• Alkylating agents (link DNA strands to prevent DNA replication), 
• Antimetabolites (act on enzymes needed to synthesise molecules essential for cell growth and replication), 
• Plant alkaloids (block microtubule function needed for cell division),
• Topoisomerase inhibitors (disrupt normal DNA coiling patterns) 
• Antitumour antibiotics (interfere with proper DNA and RNA function) 
• Targeted therapies include monoclonal antibodies that can bind to precise targets and inhibitors of particular kinase enzymes. 

Many cancers that were previously fatal can now be treated.

Description of the article image: Vinblastine and vincristine, drugs derived from the plant Catharanthus roseus, are used as chemotherapeutic agents to treat leukaemia and other cancers. 

Historical figures mentioned in the article: Sidney Farber (1903 – 1973), Louis S. Goodman (1906 – 2000), Alfred Gilman (1908 – 1984)

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