Drug repositioning for gynecologic tumors: a new therapeutic strategy for cancer
| Autor: | Megumi Yanokura, Haruko Irie, Kenta Masuda, Kouji Banno, Miho Iida, Eiichiro Tominaga, Daisuke Aoki, Yusuke Kobayashi |
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| Rok vydání: | 2014 |
| Předmět: |
Drug
Combination therapy Genital Neoplasms Female media_common.quotation_subject Peroxisome Proliferator-Activated Receptors lcsh:Medicine Review Article Pharmacology AMP-Activated Protein Kinases lcsh:Technology General Biochemistry Genetics and Molecular Biology Therapeutic index Pharmacokinetics medicine Humans lcsh:Science General Environmental Science media_common Ritonavir Cyclooxygenase 2 Inhibitors lcsh:T Drug discovery business.industry lcsh:R Drug Repositioning Cancer General Medicine medicine.disease Metformin Drug repositioning lcsh:Q Drug Therapy Combination Female Ovarian cancer business |
| Zdroj: | The Scientific World Journal The Scientific World Journal, Vol 2015 (2015) |
| ISSN: | 1537-744X |
| Popis: | The goals of drug repositioning are to find a new pharmacological effect of a drug for which human safety and pharmacokinetics are established and to expand the therapeutic range of the drug to another disease. Such drug discovery can be performed at low cost and in the short term based on the results of previous clinical trials. New drugs for gynecologic tumors may be found by drug repositioning. For example, PPAR ligands may be effective against ovarian cancer, since PPAR activation eliminates COX-2 expression, arrests the cell cycle, and induces apoptosis. Metformin, an antidiabetic drug, is effective for endometrial cancer through inhibition of the PI3K-Akt-mTOR pathway by activating LKB1-AMPK and reduction of insulin and insulin-like growth factor-1 due to AMPK activation. COX-2 inhibitors for cervical cancer may also be examples of drug repositioning. PGE2 is induced in the arachidonate cascade by COX-2. PGE2 maintains high expression of COX-2 and induces angiogenic factors including VEGF and bFGF, causing carcinogenesis. COX-2 inhibitors suppress these actions and inhibit carcinogenesis. Combination therapy using drugs found by drug repositioning and current anticancer drugs may increase efficacy and reduce adverse drug reactions. Thus, drug repositioning may become a key approach for gynecologic cancer in drug discovery. |
| Databáze: | OpenAIRE |
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