Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposis sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used together with other chemotherapy agents. Doxorubicin is given by injection into a vein.Common side effects include hair loss, bone marrow suppression, vomiting, rash, and inflammation of the mouth. Other serious side effects may include allergic reactions such as anaphylaxis, heart damage, tissue damage at the site of injection, radiation recall, and treatment-related leukemia. People often experience red discoloration of the urine for a few days. Doxorubicin is in the anthracycline and antitumor antibiotic family of medications. It works in part by interfering with the function of DNA.Doxorubicin was approved for medical use in the United States in 1974. It is on the World Health Organizations List of Essential Medicines. Versions that are pegylated and in liposomes are also available; however, they are more expensive. Doxorubicin was originally made from the bacterium Streptomyces peucetius. Medical uses
In the EU doxorubicin pegylated liposomal (as Caelyx) is indicated to treat breast cancer, ovarian cancer, and AIDS-related Kaposis sarcoma. It is indicated to treat multiple myeloma in combination with bortezomib. Doxorubicin hydrochloride (as Myocet liposomal) is indicated to treat breast cancer in combination with cyclophosphamide.Doxorubicin is commonly used to treat some leukemias and Hodgkins lymphoma, as well as cancers of the bladder, breast, stomach, lung, ovaries, thyroid, soft tissue sarcoma, multiple myeloma, and others.
Some triple mutants, that also over-expressed dox A, were able to double the yield of DXR. This is of more than academic interest, because at that time DXR cost about $1.37 million per kg and current production in 1999 was 225 kg per annum.More efficient production techniques have brought the price down to $1.1 million per kg for the nonliposomal formulation. Although DXR can be produced semi-synthetically from daunorubicin, the process involves electrophilic bromination and multiple steps, and the yield is poor. Since daunorubicin is produced by fermentation, it would be ideal if the bacteria could complete DXR synthesis more effectively. Mechanism of action
Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of topoisomerase II, an enzyme which relaxes supercoils in DNA for transcription. Doxorubicin stabilizes the topoisomerase II complex after it has broken the DNA chain for replication, preventing the DNA double helix from being released and thereby stopping the process of replication. It may also increase quinone type free radical production, hence contributing to its cytotoxicity.The planar aromatic chromophore portion of the molecule intercalates between two base pairs of the DNA, while the six-membered daunosamine sugar sits in the minor groove and interacts with flanking base pairs immediately adjacent to the intercalation site, as evidenced by several crystal structures.By intercalation, doxorubicin can also induce histone eviction from transcriptionally active chromatin. As a result, DNA damage response, epigenome and transcriptome are deregulated in doxorubicin-exposed cells.