Doxorubicin is a cytotoxic anthracycline antibiotic isolated from cultures of Streptomyces peucetius var. caesius along side with daunorubicin, another cytotoxic agent, in 1970.[A1575,A257709,A257614] Although they both have aglyconic and sugar moieties, doxorubicin's side chain terminates with a primary alcohol group compared to the methyl group of daunorubicin.[A257709] Although its detailed molecular mechanisms have yet to be understood, doxorubicin is generally thought to exert its effect through DNA intercalation, which eventually leads to DNA damage and the generation of reactive oxygen species.[A257614] Thanks to its efficacy and broad effect, doxorubicin was approved by the FDA in 1974 to treat a variety of cancer, including but not limited to breast, lung, gastric, ovarian, thyroid, non-Hodgkin’s and Hodgkin’s lymphoma, multiple myeloma, sarcoma, and pediatric cancers.[A1573,A257614,L45231] However, one of the major side effects of doxorubicin is cardiotoxicity, which excludes patients with poor heart function and requires treatment termination once the maximally tolerated cumulative dose is reached.[A257719]
Doxorubicin is indicated for the treatment of neoplastic conditions like acute lymphoblastic leukemia, acute myeloblastic leukemia, Hodgkin and non-Hodgkin lymphoma, metastatic breast cancer, metastatic Wilms’ tumor, metastatic neuroblastoma, metastatic soft tissue and bone sarcomas, metastatic ovarian carcinoma, metastatic transitional cell bladder carcinoma, metastatic thyroid carcinoma, metastatic gastric carcinoma, and metastatic bronchogenic carcinoma.[L45231] Doxorubicin is also indicated for use as a component of adjuvant therapy in women with evidence of axillary lymph node involvement following resection of primary breast cancer.[L45231] For the liposomal formulation, doxorubicin is indicated for the treatment of ovarian cancer that has progressed or recurred after platinum-based chemotherapy, AIDS-Related Kaposi's Sarcoma after the failure of prior systemic chemotherapy or intolerance to such therapy, and multiple myeloma in combination with bortezomib in patients who have not previously received bortezomib and have received at least one prior therapy.[L45226]
Categories
Anthracycline Topoisomerase Inhibitor
Anthracyclines
Anthracyclines and Related Substances
Antibiotics, Antineoplastic
Antineoplastic Agents
Antineoplastic and Immunomodulating Agents
BCRP/ABCG2 Substrates
BSEP/ABCB11 Substrates
BSEP/ABCB11 Substrates with a Narrow Therapeutic Index
Drug Info/Drug Targets: DrugBank 3.0: a comprehensive resource for 'omics' research on drugs. Knox C, Law V, Jewison
T, Liu P, Ly S, Frolkis A, Pon A, Banco K, Mak C, Neveu V, Djoumbou Y, Eisner R, Guo AC, Wishart DS.
Nucleic Acids Res. 2011 Jan; 39 (Database issue):D1035-41. | PMID:21059682
