2020
DOI: 10.1155/2020/7180923
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Metformin: A Possible Option in Cancer Chemotherapy

Abstract: Metformin has been used for a long time as an antidiabetic medication for type 2 diabetes. It is used either as a monotherapy or in combination with other antidiabetic medications. The drug came into prominence in diabetes and other conditions with cardiovascular risk after the landmark study of 1995 by the United Kingdom Prospective Diabetes Study which emphasized its importance. However, the drug has been used in experimental trials in various aspects of medicine and pharmacology such as in reproductive medi… Show more

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Cited by 42 publications
(26 citation statements)
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“…Unfortunately, BEZ-235 (Dactolisib) showed high toxicity levels in preclinical studies and the completed clinical trials so far have not obtained any benefits [65] . On the contrary, metformin (Glucophage), which indirectly inhibits mTORC1 through activation of the adenosine monophosphate protein kinase (AMPK) [66] , has obtained promising results and is currently ongoing several clinical trials in breast cancer (NCT01101438), endometrial cancer (NCT01697566), colorectal cancer (NCT02614339), prostate cancer (NCT01864096) and oral cancer (NCT03685409 and NCT02581137). Differently to metformin, rapamycin (Rapamune) is an allosteric inhibitor that directly inhibits mTOR by binding to its FKBP-rapamycin-binding (FRB) domain and so far, encouraging results have been obtained in preclinical and clinical studies in prostate cancer patients [ 44 , 67 ].…”
Section: Available Strategies To Target Tumor Hypoxiamentioning
confidence: 99%
“…Unfortunately, BEZ-235 (Dactolisib) showed high toxicity levels in preclinical studies and the completed clinical trials so far have not obtained any benefits [65] . On the contrary, metformin (Glucophage), which indirectly inhibits mTORC1 through activation of the adenosine monophosphate protein kinase (AMPK) [66] , has obtained promising results and is currently ongoing several clinical trials in breast cancer (NCT01101438), endometrial cancer (NCT01697566), colorectal cancer (NCT02614339), prostate cancer (NCT01864096) and oral cancer (NCT03685409 and NCT02581137). Differently to metformin, rapamycin (Rapamune) is an allosteric inhibitor that directly inhibits mTOR by binding to its FKBP-rapamycin-binding (FRB) domain and so far, encouraging results have been obtained in preclinical and clinical studies in prostate cancer patients [ 44 , 67 ].…”
Section: Available Strategies To Target Tumor Hypoxiamentioning
confidence: 99%
“…For example, sirolimus, an mTOR inhibitor has shown encouraging results in preclinical and clinical studies in prostate cancer [ 164 , 165 ]. Furthermore, metformin indirectly inhibits mTORC1 through activation of the AMPK pathway and has also demonstrated promising results [ 166 ]. Furthermore, in preclinical models, metformin has been linked to increased T cell activation, working synergistically with checkpoint blockade [ 167 ].…”
Section: Targeting Hypoxia and Hifs In Cancermentioning
confidence: 99%
“…The finding that patients with diabetes taking metformin, but not other anti-diabetic drugs, have a decreased risk of dying from PC [11,12] led to extensive studies on the anti-tumor effects of metformin in PC. Pre-clinical studies demonstrate that metformin can down-regulate AR by disrupting the protein midline-1 (MID1) complex, which otherwise increases AR via enhanced translation [13].…”
Section: Introductionmentioning
confidence: 99%