PMID- 25455733
OWN - NLM
STAT- MEDLINE
DCOM- 20150419
LR  - 20190108
IS  - 1095-6859 (Electronic)
IS  - 0090-8258 (Print)
IS  - 0090-8258 (Linking)
VI  - 135
IP  - 3
DP  - 2014 Dec
TI  - Old drug, new trick: repurposing metformin for gynecologic cancers?
PG  - 614-21
LID - S0090-8258(14)01371-7 [pii]
LID - 10.1016/j.ygyno.2014.10.011 [doi]
AB  - OBJECTIVE: There is increasing pre-clinical and clinical evidence that metformin, 
      a commonly used diabetes medication, has a protective effect in cancer. The aim 
      of this review is to discuss metformin's anti-cancer molecular mechanisms of 
      action and to summarize the current literature demonstrating metformin's 
      potential in gynecologic cancer prevention and treatment. METHODS: A PubMed 
      search was conducted combining the keywords "metformin" with "neoplasm", "uterine 
      neoplasms", "ovarian neoplasms", and "uterine cervical neoplasms". Studies 
      published in English between 1994 and 2014 were included. RESULTS: Pre-clinical 
      studies in endometrial, ovarian, and cervical cancer suggest that metformin 
      inhibits the growth of cancer cells. The primary molecular mechanism mediating 
      this effect appears to be the activation of AMP-activated protein kinase (AMPK) 
      and the subsequent inhibition of mammalian targets of rapamycin (mTOR). The 
      pre-clinical findings are augmented by clinical studies indicating that metformin 
      use is associated with a reduced risk of cancer and improved survival in diabetic 
      women with ovarian and endometrial cancers. No clinical analyses have evaluated 
      metformin use and cervical cancer. Overall, the data showing a favorable effect 
      of metformin is strongest for endometrial and ovarian cancer and prospective 
      clinical testing is ongoing in these two malignancies. CONCLUSIONS: Numerous 
      clinical studies have reported an association between metformin use by diabetic 
      patients and improved outcomes in gynecologic cancers. In addition, pre-clinical 
      reports have identified plausible biological mechanisms to explain the molecular 
      mechanism of action of metformin in cancer. However, the most important question 
      remains unanswered: Will metformin be effective against cancer in patients 
      without diabetes? Until this question is answered with prospective clinical 
      testing, the role of metformin in the treatment or prevention of gynecologic 
      malignancies remains theoretical and the clinical use of metformin as a cancer 
      therapeutic is experimental.
CI  - Copyright (c) 2014 Elsevier Inc. All rights reserved.
FAU - Febbraro, Terri
AU  - Febbraro T
AD  - Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, USA.
FAU - Lengyel, Ernst
AU  - Lengyel E
AD  - Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, USA.
FAU - Romero, Iris L
AU  - Romero IL
AD  - Department of Obstetrics and Gynecology, University of Chicago, Chicago, IL, USA. 
      Electronic address: iromero@uchicago.edu.
LA  - eng
GR  - UL1 TR000430/TR/NCATS NIH HHS/United States
GR  - K12 HD000849/HD/NICHD NIH HHS/United States
GR  - R01 CA111882/CA/NCI NIH HHS/United States
GR  - 5R01CA111882-07/CA/NCI NIH HHS/United States
GR  - 1R01CA169604-01A1/CA/NCI NIH HHS/United States
GR  - 2K12HD000849-26/HD/NICHD NIH HHS/United States
GR  - R01 CA169604/CA/NCI NIH HHS/United States
GR  - P50 CA136393/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20141023
PL  - United States
TA  - Gynecol Oncol
JT  - Gynecologic oncology
JID - 0365304
RN  - 9100L32L2N (Metformin)
SB  - IM
MH  - Female
MH  - Genital Neoplasms, Female/*prevention & control
MH  - Humans
MH  - Metformin/*administration & dosage
PMC - PMC4268303
MID - NIHMS640356
OTO - NOTNLM
OT  - Endometrial cancer
OT  - Glucose
OT  - Gynecologic cancer
OT  - Metformin
OT  - Ovarian cancer
EDAT- 2014/12/03 06:00
MHDA- 2015/04/22 06:00
PMCR- 2015/12/01
CRDT- 2014/12/03 06:00
PHST- 2014/07/24 00:00 [received]
PHST- 2014/10/07 00:00 [revised]
PHST- 2014/10/13 00:00 [accepted]
PHST- 2014/12/03 06:00 [entrez]
PHST- 2014/12/03 06:00 [pubmed]
PHST- 2015/04/22 06:00 [medline]
PHST- 2015/12/01 00:00 [pmc-release]
AID - S0090-8258(14)01371-7 [pii]
AID - 10.1016/j.ygyno.2014.10.011 [doi]
PST - ppublish
SO  - Gynecol Oncol. 2014 Dec;135(3):614-21. doi: 10.1016/j.ygyno.2014.10.011. Epub 
      2014 Oct 23.