Also called:
antineoplastic drug
Key People:
George Herbert Hitchings
Gertrude B. Elion

anticancer drug, any drug that is effective in the treatment of malignant, or cancerous, disease. There are several major classes of anticancer drugs; these include alkylating agents, antimetabolites, natural products, and hormones. In addition, there are a number of drugs that do not fall within those classes but that demonstrate anticancer activity and thus are used in the treatment of malignant disease. The term chemotherapy frequently is equated with the use of anticancer drugs, although it more accurately refers to the use of chemical compounds to treat disease generally.

One of the first drugs that was used clinically in modern medicine for the treatment of cancer was the alkylating agent mechlorethamine, a nitrogen mustard that in the 1940s was found to be effective in treating lymphomas. In 1956 the antimetabolite methotrexate became the first drug to cure a solid tumour, and the following year 5-fluorouracil was introduced as the first of a new class of tumour-fighting compounds known as pyrimidine analogs. Since then many anticancer drugs have been developed and used with much success.

The decision to use a certain anticancer drug depends on many factors, including the type and location of the cancer, its severity, whether surgery or radiation therapy can or should be used, and the side effects associated with the drug. Most anticancer drugs are administered intravenously; however, some can be taken orally, and others can be injected intramuscularly or intrathecally (within the spinal cord).

Gleevec; imatinib
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drug: Anticancer drugs

The treatment of cancer is complicated in that the drugs used target human cells, albeit cells that have undergone genetic changes and are dividing at a fast and uncontrolled rate. However, certain anticancer drugs can differentiate to some degree between normal tissue cells and cancer cells, and the rate at which cancer cells proliferate may in fact play a role in the apparent selectivity of agents. For instance, alkylating agents, which act on cells at all stages of the cell cycle, appear to be most toxic to cells in the synthesis, or S, stage, when DNA is in the process of replicating and unpaired nucleotides (the nitrogen-containing units of DNA and RNA) are most vulnerable to alkylation (the addition of an alkyl group). In the late 20th and early 21st centuries, the identification of molecular features unique to cancer cells fueled the development of targeted cancer therapies, which possess a relatively high degree of specificity for cancer cells.

The specificity of anticancer drugs plays an important role in reducing the severity of side effects associated with the drugs’ use. Indeed, because cancer cells are similar to normal human cells, anticancer agents are generally toxic to normal cells and can cause numerous side effects, some of which are life-threatening. Such side effects include hair loss, sores in the mouth and on other mucous membranes, cardiac anomalies, bone marrow toxicity, and severe nausea and vomiting. The bone marrow toxicities result in anemia as well as in decreased resistance to infectious agents. Permanent infertility can also result. Those adverse effects may require that the drug dosage be reduced or the drug regimen be changed to make the drug tolerable to the patient.

In rare instances prolonged use of anticancer drugs can lead to the development of secondary cancers. The type of agent, the primary cancer that it is used to treat, and the total cumulative dose administered influence the extent to which an anticancer drug is carcinogenic (cancer-causing). Frequently occurring secondary cancers associated with anticancer drug therapy are myelodysplastic syndrome and acute leukemias, risk of which is increased particularly with the use of alkylating agents and topoisomerase inhibitors (e.g., etoposide).

The side effects associated with anticancer drugs can be reduced through the use of multiple agents, which often enables the administration of lower dosages of each drug. The use of multiple agents may also reduce the incidence of cellular resistance, a phenomenon that allows tumours to escape treatment and to continue to grow after a period of remission (absence of disease activity). Multidrug therapy is based on the premise that different types of anticancer drugs exert their effects in a certain part of the cell cycle (e.g., cell growth phase, cell division phase, resting phase). Thus, one drug may be used to stop the growth of cancer cells in a certain phase, while another agent may work at a different phase. In addition to using complex regimens that employ several drugs, cancer chemotherapy is often combined with surgery to reduce the number of cancer cells and with radiation treatment to destroy more cells.

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Irvin S. Snyder Janet L. Stringer The Editors of Encyclopaedia Britannica

chemotherapy, the treatment of diseases by chemical compounds. Chemotherapeutic drugs were originally those employed against infectious microbes, but the term has been broadened to include anticancer and other drugs.

Until the end of the 19th century, most drugs were derived either from minerals or from plants. The researches of Louis Pasteur in France and Robert Koch in Germany laid the foundations of bacteriology. It was Paul Ehrlich, however, who made the greatest contribution to the science (chemotherapy) he named. The problem facing medical scientists was to produce a disinfectant that would destroy parasites within a living animal without serious damage to the host.

William H. Perkin, in England, made the first aniline dye (1856) as a result of abortive attempts to synthesize quinine, the sole antimalarial drug available at that time. About 30 years later, Ehrlich found that a synthetic dye, methylene blue, has antimalarial properties. He had been led to this by a study of the specific staining of organs of an animal or of a parasite following the injection of a synthetic dye. From these studies there emerged (1901–04) Ehrlich’s well-known “side-chain” theory, in which he sought for the first time to correlate the chemical structure of a synthetic drug with its biological effects. In 1903 Ehrlich invented a dye, trypan red, which was the first drug to show activity against trypanosomal infections in mice. Ehrlich’s greatest triumph, however, was the discovery (1910) of the organic arsenical drug Salvarsan, which proved to be effective in the treatment of syphilis. The discovery of other chemotherapeutic agents followed, including mepacrine, proguanil, and chloroquine.

Prozac
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therapeutics: Chemotherapy

The discovery of Prontosil in the early 1930s proved that antibacterial agents could be developed. Prontosil was the forerunner of the sulfonamide drugs, which came to be widely used for the treatment of bacterial infections in humans and domestic animals.

The discovery of penicillin by Sir Alexander Fleming in 1928, and its practical development by Sir Howard Florey and Ernst Chain, marked another important advance in bacterial chemotherapy. Penicillin, which did not become widely used until World War II, was the first of the so-called antibiotics, and it was followed by other important antibiotics such as streptomycin, the tetracyclines, and the macrolides.

Antibiotics, whether they are produced by living organisms (usually fungi or bacteria) or artificially synthesized, have transformed the modern management of diseases caused by bacteria and most other microorganisms. Paradoxically, the more widely they are used, the greater the likelihood that drug-resistant bacteria will emerge. Bacteria may develop resistance to drugs in several ways: mutation changes in genetic composition; transduction, whereby resistance is transferred from a resistant to a nonresistant strain; transformation, in which a bacterial cell takes from its environment the genes from a resistant form to acquire resistance; and conjugation, in which the organism acquires resistance by cell-to-cell contact.

Another comparative failure of chemotherapy is the lack of drugs to combat viruses (although viral infections can be controlled through prophylactic measures).

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Drug modes of action vary. For example, some may act on the bacterial wall, others affect cell membranes, some modify the molecular mechanism for duplication, some change the nucleic acid metabolism, and others change the intermediary metabolism of two interacting organisms.

Cancer chemotherapy is an increasingly important aspect of drug treatment. Alkylating agents (that work by impairing cell division) and antimetabolites (that interfere with enzymes and thus block vital cell processes) are used cytotoxically to attack malignant cells. Steroid hormones are used in the treatment of breast and prostate cancers, and corticosteroids are used to treat leukemia and lymphatic cancers. The periwinkle plant derivatives vincristine and vinblastine have been used effectively in treating Hodgkin’s disease and leukemia.

The alkylating agents and antimetabolites have serious drawbacks. As they cannot distinguish between healthy and malignant cells, these drugs also interfere with actively multiplying noncancerous cells. They also reduce the body’s resistance to infection. Work is being done on tumour-specific agents that attack only cancer cells.

Another area where chemotherapy has had a major, albeit controversial, impact is mental illness. Severe depression, anxiety, and schizophrenia are now treated with various drugs.

Concomitant with the successes of drug therapy has come increasing concern about attendant dangers. Stringent controls are operated by such regulatory agencies as the Food and Drug Administration in the United States and the Committee on Safety of Medicines in the United Kingdom. These bodies ensure the safety of pharmaceuticals before they are placed on the market and monitor any side effects thereafter. Public demands for “watchdog” agencies were triggered in large part by the 1962 Thalidomide tragedy, when thousands of severely deformed children were born to users of that insufficiently tested drug.

The Editors of Encyclopaedia Britannica This article was most recently revised and updated by Kara Rogers.