angiogenesis inhibitor
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angiogenesis inhibitor
n.
A drug that blocks angiogenesis in cancerous tissue, thus interfering with tumor growth or metastasis.
Gale Encyclopedia of Cancer:
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Angiogenesis Inhibitors
Definition
Angiogenesis inhibitors are medicines that stop the formation of new blood vessels in and around cancerous tumors.
Description
Angiogenesis inhibitors are a group of medicines that prevent the formation of tiny new blood vessels to the area of cancerous tumors. Angiogenesis refers to the ability of cancer cells to form new blood vessels that invade the tumor and other surrounding areas. Tumors need a blood supply to nourish the cancer cells, and as tumors grow they must constantly form new blood vessels. These blood vessels are also used by the cancer cells to metastasize or spread the cancerous cells from one area to the next. Angiogenesis inhibitors are important because the scientific theory is that if one can remove and/or prevent the formation of new blood vessels in the tumors, the cancer cells will not be able to grow any further. This could cause the tumors to stay the same size or shrink. In addition, it may be possible to prevent the tumors from spreading by cutting off their ability to invade other surrounding areas through these newly formed blood vessels. There are a few drugs today thought to work as angiogenesis inhibitors, such as thalidomide. Additional agents being studied in ongoing oncology clinical trials.
—Nancy J. Beaulieu, RPh., BCOP
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Angiogenesis inhibitor
An angiogenesis inhibitor is a substance that inhibits the growth of new blood vessels (angiogenesis). Some angiogenesis inhibitors are a normal part of the body's control, some are administered as drugs, and some come from diet.
Angiogenesis inhibitors were once thought to have potential as a "silver bullet" treatment applicable to many types of cancer, but this has not been the case in practice.[1] Nonetheless, inhibitors are used to treat cancer, macular degeneration in the eye, and other diseases that involve a proliferation of blood vessels.
When solid cancers are small, they are supplied with nutrients by diffusion from nearby blood vessels. In order to grow larger, they need their own blood vessels, which they create by angiogenesis promoters such as VEGF. Drugs that interrupt that process show promise in treating cancer. However, when one angiogenesis promoter is blocked, cancers eventually grow blood vessels using another angiogenesis promoter.
Angiogenesis inhibitors are also used to treat age-related macular degeneration, in which the blood vessels of the retina of the eye become overgrown and damage vision.
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Contents
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Endogenous
Exogenous
Exogenous angiogenesis inhibitors may be drugs or a dietary components. Some of them are endogenous as well.
Drugs
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This unreferenced section requires citations to ensure verifiability. |
Known inhibitors include the drug bevacizumab (brand name Avastin), a kind of humanized mouse monoclonal antibody against vascular endothelial growth factor (VEGF)
Through binding to VEGFR and other VEGF receptors in endothelial cells, VEGF can trigger multiple cellular responds like promoting cell survival, preventing apoptosis, and remodeling cytoskeleton, all of which promote angiogenesis.
Because it traps VEGF in the blood, bevacizumab is an anti-angiogenesis factor. Lowering the concentration of VEGF results in reduced activation of the angiogenesis pathway, thus inhibiting new blood vessel formation in tumors.
Research and development in this field has been driven largely by the desire to find better cancer treatments. Tumors cannot grow larger than 2mm without angiogenesis. By stopping the growth of blood vessels, scientists hope to cut the means by which tumors can nourish themselves and thus metastasizing. After a series of clinical trials in 2004, Avastin got approval from the FDA, becoming the first commercially available anti-angiogenesis drug. FDA approval for breast cancer was later revoked on November 18, 2011.
Despite the therapeutic potential of anti-angiogenesis drugs, they also bring disasters when used inappropriately. The pharmaceutical thalidomide is such an antiangiogenic agent. When pregnant women take an antiangiogenic agent, the developing fetus will not form blood vessels properly, thereby preventing the proper development of fetal limbs and circulatory systems. In the late 1950s and early 1960s, more than 10,000 children in 46 countries were born with deformities, most notably phocomelia, as a consequence of thalidomide use.
In addition to their use as anti-cancer drugs, angiogenesis inhibitors are being investigated for their use as anti-obesity agents, as blood vessels in adipose tissue never fully mature, and are thus destroyed by angiogenesis inhibitors.
Matrix metalloproteinase inhibitors that may be antiangiogenic are batimastat and marimastat.
According to a study published in the August 15, 2004 issue of the journal Cancer Research, cannabinoids, the active ingredients in marijuana, restrict the sprouting of blood vessels to brain tumors by inhibiting the expression of genes needed for the production of vascular endothelial growth factor (VEGF).[3]
Summary
| Inhibitors | Antiangiogenic use in |
Mechanism |
|---|---|---|
| bevacizumab | Cancer | binds VEGF |
| itraconazole | Cancer | inhibits VEGFR phosphorylation, glycosylation, mTOR signaling, endothelial cell proliferation, cell migration, tube formation, and tumor associated angiogenesis.[4][5][6] |
| carboxyamidotriazole | inhibit cell proliferation and cell migration of endothelial cells | |
| TNP-470 | ||
| CM101 | activate immune system | |
| IFN-α | downregulate angiogenesis stimulators and inhibit cell migration of endothelial cells | |
| IL-12 | stimulate angiogenesis inhibitor formation | |
| platelet factor-4 | inhibits binding of angiogenesis stimulators | |
| suramin | prostate cancer | |
| SU5416 | ||
| thrombospondin | ||
| VEGFR antagonists | ||
| angiostatic steroids + heparin | inhibit basement membrane degradation | |
| Cartilage-Derived Angiogenesis Inhibitory Factor | ||
| matrix metalloproteinase inhibitors | ||
| angiostatin | inhibit cell proliferation and induce apoptosis of endothelial cells | |
| endostatin | inhibit cell migration, cell proliferation and survival of endothelial cells | |
| 2-methoxyestradiol | inhibit cell proliferation and cell migration and induce apoptosis of endothelial cells | |
| tecogalan | inhibit cell proliferation of endothelial cells | |
| tetrathiomolybdate | Cancer | copper chelation which inhibits blood vessel growth |
| thalidomide | inhibit cell proliferation of endothelial cells | |
| thrombospondin | inhibit cell migration, cell proliferation, cell adhesion and survival of endothelial cells | |
| prolactin | inhibit bFGF and VEGF | |
| αVβ3 inhibitors | induce apoptosis of endothelial cells | |
| linomide | inhibit cell migration of endothelial cells | |
| tasquinimod | prostate cancer | Unknown[7] |
Diet
Some common components of human diets also act as mild angiogenesis inhibitors and have therefore been proposed for angioprevention, the prevention of metastasis through the inhibition of angiogenesis. In particular, the following foodstuffs contain significant inhibitors and have been suggested as part of a healthy diet for this and other benefits:
- Soy products such as tofu and tempeh, (which contain the inhibitor "genistein")[8]
- Agaricus blazei mushrooms (angiogenesis inhibitors found in the mushroom include sodium pyroglutamate and ergosterol)[9][10]
- Black raspberry extract (Rubus occidentalis)[11]
- Reishi mushrooms (via inhibition of VEGF and TGF-beta)[12]
- Trametes versicolor mushrooms[13]
- Maitake mushrooms (via inhibition of VEGF)[14]
- Phellinus linteus mushrooms[15]
- Green tea (catechins)[16]
- Liquorice (glycyrrhizic acid)[17]
- Red Wine (resveratrol)[17]
- Antiangiogenic phytochemicals and medicinal herbs.[18]
- Royal Jelly[19]
References
- ^ Hayden, Erika C. (2009-04-08). "Cutting off cancer's supply lines". Nature 458 (7239): 686–687. doi:10.1038/458686b. PMID 19360048.
- ^ Hugo H. Marti, "Vascular Endothelial Growth Factor", Madame Curie Bioscience Database (Landes Bioscience), http://www.ncbi.nlm.nih.gov/books/NBK6149/, retrieved January 25, 2012
- ^ Cristina Blázquez, Luis González-Feria, Luis Álvarez, Amador Haro, M. Llanos Casanova, and Manuel Guzmán (August 15, 2004). "Cannabinoids Inhibit the Vascular Endothelial Growth Factor Pathway in Gliomas". Cancer Res: 5617–5623. doi:10.1158/0008-5472.CAN-03-3927.
- ^ Chong, Curtis R.; Xu, Jing; Lu, Jun; Bhat, Shridhar; Sullivan, David J.; Liu, Jun O. (2007). "Inhibition of Angiogenesis by the Antifungal Drug Itraconazole". ACS Chemical Biology 2 (4): 263–70. doi:10.1021/cb600362d. PMID 17432820.
- ^ Aftab, B. T.; Dobromilskaya, I.; Liu, J. O.; Rudin, C. M. (2011). "Itraconazole Inhibits Angiogenesis and Tumor Growth in Non-Small Cell Lung Cancer". Cancer Research 71 (21): 6764–72. doi:10.1158/0008-5472.CAN-11-0691. PMC 3206167. PMID 21896639. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=3206167.
- ^ Xu, J.; Dang, Y.; Ren, Y. R.; Liu, J. O. (2010). "Cholesterol trafficking is required for mTOR activation in endothelial cells". Proceedings of the National Academy of Sciences 107 (10): 4764–9. doi:10.1073/pnas.0910872107. PMC 2842052. PMID 20176935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2842052.
- ^ Evolving Therapeutic Paradigms for Advanced Prostate Cancer. 2011. http://www.cancernetwork.com/prostate-cancer/content/article/10165/1859200?pageNumber=3.
- ^ Farina HG, Pomies M, Alonso DF, Gomez DE (October 2006). "Antitumor and antiangiogenic activity of soy isoflavone genistein in mouse models of melanoma and breast cancer". Oncol. Rep. 16 (4): 885–91. PMID 16969510. http://www.spandidos-publications.com/or/article.jsp?article_id=or_16_4_885.
- ^ Takaku T, Kimura Y, Okuda H (May 2001). "Isolation of an antitumor compound from Agaricus blazei Murill and its mechanism of action". J. Nutr. 131 (5): 1409–13. PMID 11340091.
- ^ Kimura, Y; Kido, T; Takaku, T; Sumiyoshi, M; Baba, K (2004). "Isolation of an anti-angiogenic substance from Agaricus blazei Murill: its antitumor and antimetastatic actions". Cancer Sci 95 (9): 758–764. doi:10.1111/j.1349-7006.2004.tb03258.x. PMID 15471563.
- ^ Liu, Zhijun.; Schwimer, Joshua.; Liu, Dong.; Greenway, Frank L.; Anthony, Catherine T.; Woltering, Eugene A. Black Raspberry Extract and Fractions Contain Angiogenesis Inhibitors. ACS Publications.
- ^ Stanley, Gwenaelle; Harvey, Kevin; Slivova, Veronika; Jiang, Jiahua; Sliva, Daniel (2005). "Ganoderma lucidum suppresses angiogenesis through the inhibition of secretion of VEGF and TGF-β1 from prostate cancer cells". Biochemical and Biophysical Research Communications 330 (1): 46–52. doi:10.1016/j.bbrc.2005.02.116. PMID 15781230.
- ^ Kobayashi, H; Matsunaga, K; Oguchi, Y (1995). "Antimetastatic effects of PSK (Krestin), a protein-bound polysaccharide obtained from basidiomycetes: An overview". Cancer epidemiology, biomarkers & prevention 4 (3): 275–81. PMID 7606203.
- ^ Lee, Jong-Suk; Park, Byung Chul; Ko, Yu Jin; Choi, Mi Kyoung; Choi, Han Gon; Yong, Chul Soon; Lee, Jae-Sung; Kim, Jung-Ae (2008). "Grifola frondosa(Maitake Mushroom) Water Extract Inhibits Vascular Endothelial Growth Factor-Induced Angiogenesis Through Inhibition of Reactive Oxygen Species and Extracellular Signal-Regulated Kinase Phosphorylation". Journal of Medicinal Food 11 (4): 643–51. doi:10.1089/jmf.2007.0629. PMID 19053855.
- ^ Sliva, D, Jedinak, A, Kawasaki, J, Harvey, K, Slivova, V (2008). "Phellinus linteus suppresses growth, angiogenesis and invasive behaviour of breast cancer cells through the inhibition of AKT signalling". British Journal of Cancer 98 (8): 1348–1356. doi:10.1038/sj.bjc.6604319. PMC 2361714. PMID 18362935. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2361714.
- ^ Rodriguez, Shaun K.; Guo, Weimin; Liu, Liping; Band, Michael A.; Paulson, Eric K.; Meydani, Mohsen (2006). "Green tea catechin, epigallocatechin-3-gallate, inhibits vascular endothelial growth factor angiogenic signaling by disrupting the formation of a receptor complex". International Journal of Cancer 118 (7): 1635–44. doi:10.1002/ijc.21545.
- ^ a b Smith, Roderick. Antiangiogenic Substances in Blackberries, Licorice May Aid Cancer Prevention. The Angiogenesis Foundation. 6 May 2009.[unreliable medical source?]
- ^ Jeong, Soo-Jin; Koh, Wonil; Lee, Eun-Ok; Lee, Hyo-Jung; Lee, Hyo-Jeong; Bae, Hyunsu; Lü, Junxuan; Kim, Sung-Hoon (2011). "Antiangiogenic phytochemicals and medicinal herbs". Phytotherapy Research 25 (1): 1–10. doi:10.1002/ptr.3224. PMID 20564543.
- ^ Izuta, Hiroshi; Chikaraishi, Yuichi; Shimazawa, Masamitsu; Mishima, Satoshi; Hara, Hideaki (2009). "10-Hydroxy-2-decenoic Acid, a Major Fatty Acid from Royal Jelly, Inhibits VEGF-Induced Angiogenesis in Human Umbilical Vein Endothelial Cells". Evidence-Based Complementary and Alternative Medicine 6 (4): 489–94. doi:10.1093/ecam/nem152. PMC 2781774. PMID 18955252. http://www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2781774.
External links
- The idea of antiangiogenesis was pioneered by Dr. Judah Folkman. See [1] and [2]
- Angiogenesis Inhibitors for Cancer - from The Angiogenesis Foundation, 23 June 2009
- Angiogenesis Inhibitors for Eye Disease - from The Angiogenesis Foundation, 23 June 2009
- Angiogenesis Inhibitors in the Treatment of Cancer - from the National Cancer Institute
- New Scientist on their use as fat-reducing drugs - from New Scientist, 10 April 2004
- MeSH Angiogenesis+Inhibitors
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American Heritage Dictionary
The American Heritage® Dictionary of the English Language, Fourth Edition Copyright © 2007, 2000 by Houghton Mifflin Company. Updated in 2009. Published by Houghton Mifflin Company. All rights reserved.
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Gale Encyclopedia of Cancer
Gale Encyclopedia of Cancer. Copyright © 2006 by The Gale Group, Inc. All rights reserved.
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