Doxorubicin; trade name Adriamycin; also known as hydroxydaunorubicin, is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA, while most serious adverse effect being life-threatening heart damage.
Doxorubicin; trade name Adriamycin; also known as hydroxydaunorubicin, is a drug used in chemotherapy for treatment of cancer.
It is an anthracycline antibiotic, closely related to the natural product
daunomycin. Like all anthracyclines,
doxorubicin works by intercalating DNA. It is commonly used in the treatment of a wide range of cancers, including hematological malignancies, many types of carcinoma, soft tissue sarcomas, some leukemias, multiple myeloma, and Hodgkin's lymphoma. The most serious adverse effect is life-threatening heart damage.
The drug is administered intravenously, in the form of hydrochloride salt. It may be sold under the brand names Adriamycin PFS, Adriamycin RDF, or Rubex.
Doxorubicin is photosensitive, thus containers are often covered by an aluminum bag and/or brown wax paper to prevent light from affecting it.
CLINICAL USE
Carcinomas
| Breast Carcinoma |
Ovarian Carcinoma |
Thyroid Carcinoma |
| Endometrial Carcinoma |
Testicular Carcinoma |
Lung Carcinoma |
Sarcomas
| Ewing's Sarcoma |
Osteosarcoma |
Rhabdomyosarcomas |
Hematologic Cancers
| Acute Leukemia |
Multiple Myeloma |
Hodgkin's Disease |
Non-Hodgkin's Lymphoma |
MECHANISM OF ACTION
Doxorubicin interacts with DNA by intercalation and inhibition of macromolecular biosynthesis. This inhibits the progression of the enzyme topoisomerase II, 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 resealed and thereby stopping the process of replication.
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.
SOURCES
- Laginha, K.M., Wendel H, De Stanchina E, Fridman J, Malina A, Ray S, Kogan S, Cordon-Cardo C, Pelletier J, Lowe S
