19 Bleomycin

19.1 Discovery and mechanism of action of Bleomycin

Bleomycin was discovered in 1966 in the bacterium Streptomyces verticillus. Bleomycin refers to a group of chemically related compounds. Bleomycin A2 and B2 are used as anticancer agents. The very complex chemical structures of Bleomycin A2 and B2 are shown in Figure 16.1. Bleomycin has several „domains“ including the DNA binding domain, the carbohydrate domain and the metal binding domain.

Chemical structures of Bleomycin A2 and B2, which differ in the DNA binding domain.

Figure 19.1: Chemical structures of Bleomycin A2 and B2, which differ in the DNA binding domain.

Bleomycin acts by inducing DNA breaks, but the exact mechanism of strand scission is unknown.

It was launched in Japan in 1969 and was approved in the US by the FDA in 1973. On average drugs take about 15 years to reach the market, but Bleomycin was introduced in the market very rapidly. This is an example of how a cancer drug reached the clinic very quickly.

19.2 Administration clinical uses and toxicities

Bleomycin may be administered by various routes including intramuscular, intrevenous, subcutaneous or intrapleural.

Bleomycin is used against Hodgkin’s lymphoma alone or in combination with Doxorubicin, since it also acts on DNA by intercalating into DNA and inhibiting topoisomerase II against Hodgkin‘s lymphoma. Bleomycin is also used to treat squamous cell carcinomas and testicular cancer.

Common toxicities include alopecia, fever and rash, a change of the skin that affects its colour. Less common toxicities include pulmunary fibrosis, which is a respiratory disease in which scars are formed in the lung tissues leading to serious breathing problems. An additional toxicity is impaired lung function.

Bibliography

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