History of Anticancer Drugs

Abstract

The origins of cancer chemotherapies can be traced back to their roots in the nineteenth century. Historically, the majority of anticancer drugs have been natural products or synthetic agents designed to target a specific function in the cell or nucleus of tumour cells. These conventional agents however typically suffer from side effects as they are administered systemically – that is, they circulate to other organs where they often exert unwanted ‘bystander’ toxicity. More recent approaches have harnessed the power of monoclonal antibodies, complex proteins which are manufactured from cells. Antibodies accumulate on and around specific cell types (by binding to antigens on the surface of cells), and a number of antibodies which target and kill specific cancer cells have now been developed as therapeutics. A related strategy is to employ the antibody as a ‘delivery vehicle’ to accumulate a conventional anticancer drug in the cancer cell. Such antibody drug conjugates hold great promise.

Key Concepts:

  • A number of plants and bacteria produce toxins which have been used successfully as anticancer drugs.

  • A major limitation of conventional anticancer drugs is that they are also toxic to healthy tissue, and result in many side effects including nausea, hair loss, bone marrow loss and irritation of the gastrointestinal tract.

  • Proteins known as monoclonal antibodies, which target individual cell types specifically, hold great promise for the treatment of certain cancers.

  • Future research will focus on personalised cancer therapeutics, where the appropriate drug is selected based on the patients genomic makeup.

  • Synthetic derivatives and mimics of natural products have become front line therapeutics against a number of cancers.

Keywords: anticancer drugs; history; natural products; monoclonal antibodies; antibody drug conjugates

References

Albanell J, Codony J, Rovira A, Mellado B and Gascon P (2003) Mechanism of action of anti‐HER2 monoclonal antibodies: scientific update on trastuzumab and 2C4. Advances in Experimental Medicine and Biology 532: 253–268.

Bross PF, Beitz J, Chewn G et al. (2001) Approval summary: gemtuzumab ozogamicin in relapsed acute myeloid leukemia. Clinical Cancer Research 7(6): 1490–1496.

Eccles SA (2001) Monoclonal antibodies targeting cancer: ‘magic bullets’ or just the trigger? Breast Cancer Research: BCR 3(2): 86–90.

Krumbhaar EB and Krumbhaar HD (1919) The blood and bone marrow in yellow cross gas (mustard gas) poisoning. Changes produced in the bone marrow of fatal cases. Journal of Medical Research 40: 497–507.

LoRusso PM, Weiss D, Guardino E, Girish S and Sliwkowski MX (2011) Trastuzumab emtansine: a unique antibody‐drug conjugate in development for human epidermal growth factor receptor 2‐positive cancer. Clinical Cancer Research 17(20): 6437–6447.

Pappenheimer AM and Vance M (1920) Effects of intravenous injections of dichloroethyl sulfide in rabbits, with special reference to its leucotoxic action. Journal of Experimental Medicine 31: 71–95.

Svoboda GH (1961) Alkaloids of Vinca rosea. IX. Extraction and characterization of leurosidine and leurocristine. Lloydia 24: 173–178.

Teicher BA and Doroshow JH (2012) The promise of antibody‐drug conjugates. The New England Journal of Medicine 367(19): 1847–1848.

Wall ME, Wani MC, Cook CE et al. (1966) Plant antitumor agents. I. Isolation and structure of camtothecin, a novel alkaloidal leukemia and tumor inhibitor from Camptotheca acuminata. Journal of the American Chemical Society 88: 3888–3890.

Wani MC, Taylor HL, Wall ME, Coggon P and McPhail AT (1971) Plant antitumor agents. VI. Isolation and structure of Taxol, a novel antileukemic and antitumor agent from Taxus brevifolia. Journal of the American Chemical Society 93: 2325–2327.

Further Reading

Bentley R (1861) A Manual of Botany Including the Structure, Function, Classification, Properties and Uses of Plants, 811 pp. London: John Churchill.

Brugge J, Curran T and Harlow S (eds) (1991) Origins of Human Cancer: A Comprehensive Review. Plainview, NY: Cold Spring Harbor Laboratory Press.

Carter S, Glatstein E and Livingston R (eds) (1982) Principles of Cancer Treatment. New York, NY: McGraw‐Hill.

Foyle WO (ed.) (1995) Cancer Chemotherapeutic Agents. Washington, DC: ACS.

Hoare RC (1977) Anthraquinone dyes. US Patent 4,051,155.

Jones GB (ed.) (1998) Advances in DNA Sequence Specific Agents, vol. 3. Greenwich, CT: JAI Press.

Scott SD (1998) Rituximab: a new therapeutic monoclonal antibody for non-Hodgkin's lymphoma. Cancer Practice 6(3): 195–197.

Wood HC, Remington JP, Sadtler SP (1899) The Dispensatory of the United States of America, 18th edn, p. 660. Philadelphia, PA: J.B. Lippincott Company.

Contact Editor close
Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite close
Jones, Graham B(Oct 2014) History of Anticancer Drugs. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0003630.pub2]