Doxorubicin
Doxorubicin is useful in a wide range of cancers, including: breast cancer, lymphomaA cancer arising in the lymphatic system. The white blood cells affected are part of the body's immune system. The lymphatic system is a large network of vessels that carry fluid and cells of the immune system around the body. Lymph nodes are regional collection centers in the lymphatic system. See also, 'lymphatic system'., soft tissue sarcomaA malignant cancer that originates in bone, muscle or connective tissues., ovarian cancer and many more. There are only a few cancer types are unresponsive to the drug, which include: colon cancer, melanoma, chronic leukemias and renal cancer. Doxorubicin is administered intravenously. In a newer formulation, Doxil, the drug is surrounded by a lipidA class of biomolecule. Lipids all share the common feature of being hydrophobic . Lipids are one of four classes of biomolecules that make up the majority of the materials in our cells. Other classes are proteins, carbohydrates and nucleic acids. 'bubble' (membrane). This formulation is an attempt to reduce the toxicity of the drug by blocking its effects on normal tissues.1
Doxorubicin is an anthracycline antibiotic that exerts its effects on cancer cells via two different mechanisms. It acts as an intercalating agent and wedges between the DNAAbbreviation for deoxyribonucleic acid. Composed of very long strings of nucleotides, which are abbreviated as A, C, G and T. DNA is the storage form of our genetic material. All of the instructions for the production of proteins are encoded in our DNA. bases thus blocking DNA synthesis and transcriptionThe production of an RNA molecule from a DNA template. An RNA copy of a gene is produced by an enzyme, RNA polymerase. The RNA produced can either be used directly in the cell or can be used to direct the production of a protein through the process of translation. Many of the genes that are altered in cancer cells have potent effects on the process of transcription. See transcription factor.. The drug also inhibits the activity of an enzymeA protein that speeds up the process of chemical reactions in the body without becoming altered in the process. Almost every biological process is driven by the activity of enzymes. Without enzyme catalysts, the complex reactions that build and break down cell parts would not happen at a rate compatible with life. Enzyme names usually describe the reaction that is being catalyzed and all of them end in -ase., topoisomeraseAn enzyme that cuts double stranded DNA to reduce tension created during local unwinding of the helix. Unwinding of DNA is required for transcription, translation and replication. Chemotherapy drugs such as topotecan and etoposide (VP-16) inhibit topoisomerases. type II. This leads to breaks in the genomic DNA. Both of these mechanisms result in DNA disruption that ultimately can lead to the death of the cell.1 Interestingly, several studies have reported that green tea enhances the antitumor activity of doxorubicin.2
Below is the structure of a 3D Doxorubicin conformer.
Common side effects include: decreased blood cell counts, increased risk of infection and bleeding, loss of appetite, stomatitis, alopecia (hair loss), Nausea and vomiting, mouth sores, Birth defects, liver toxicity, and acute arrhythmia. Cardiac toxicity becomes relevant at high doses. If present, the cardiomyopathy may lead to irreversible congestive heart failure.1 Due to this concern, patients should talk to their doctors about any cardiac conditions or complications. Slow intravenous infusion can reduce cardiac toxicity (by lowering blood concentrations of the drug). However, this method can be problematic because it lasts for 48-96 hours.2
- 1.a. b. c. Chu, E., & DeVita, V. T. (2015). Physicians' cancer chemotherapy drug manual 2015. Burlington, MA: Jones & Bartlett Learning.
- 2. Cheng, T., Liu, J., Ren, J., Huang, F., Ou, H., Ding, Y., … Shi, L. (2016). Green Tea Catechin-Based Complex Micelles Combined with Doxorubicin to Overcome Cardiotoxicity and Multidrug Resistance. Theranostics, 6(9), 1277–1292. http://doi.org/10.7150/thno.15133
- 3. Rygiel, K. (2016). Benefits of antihypertensive medications for anthracycline- and trastuzumab-induced cardiotoxicity in patients with breast cancer: Insights from recent clinical trials. Indian Journal of Pharmacology, 48(5), 490–497. http://doi.org/10.4103/0253-7613.190719
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