Drug repositioning for gynecologic tumors: a new therapeutic strategy for cancer.
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.
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Kouji
K
Banno
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Miho
0000-0001-5527-7574
M
Iida
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Megumi
M
Yanokura
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Haruko
H
Irie
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Kenta
K
Masuda
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Yusuke
Y
Kobayashi
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Eiichiro
E
Tominaga
Department of Obstetrics and Gynecology, School of Medicine, Keio University, Tokyo 160-0016, Japan.
Daisuke
D
Aoki
D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D052246:Cyclooxygenase 2 Inhibitors / Q000494:pharmacology; D058492:Drug Repositioning / Q000379:methods* / Q000639:trends*; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D005833:Genital Neoplasms, Female / Q000188:drug therapy*; D006801:Humans; D008687:Metformin / Q000494:pharmacology; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism; D019438:Ritonavir / Q000494:pharmacology
D052246:Cyclooxygenase 2 Inhibitors; D047492:Peroxisome Proliferator-Activated Receptors; D008687:Metformin; D055372:AMP-Activated Protein Kinases; D019438:Ritonavir