RT Journal Article
T1 Phenformin as an Anticancer Agent: Challenges and Prospects.
A1 García Rubiño, Mª Eugenia
A1 Carrillo, Esmeralda
A1 Ruiz Alcalá, Gloria
A1 Domínguez-Martín, Alicia
A1 A Marchal, Juan
A1 Boulaiz, Houria
K1 biguanides
K1 cancer
K1 cancer stem cells
K1 diabetes type 2
K1 phenformin
AB Currently, there is increasing evidence linking diabetes mellitus (especially type 2 diabetes mellitus) with carcinogenesis through various biological processes, such as fat-induced chronic inflammation, hyperglycemia, hyperinsulinemia, and angiogenesis. Chemotherapeutic agents are used in the treatment of cancer, but in most cases, patients develop resistance. Phenformin, an oral biguanide drug used to treat type 2 diabetes mellitus, was removed from the market due to a high risk of fatal lactic acidosis. However, it has been shown that phenformin is, with other biguanides, an authentic tumor disruptor, not only by the production of hypoglycemia due to caloric restriction through AMP-activated protein kinase with energy detection (AMPK) but also as a blocker of the mTOR regulatory complex. Moreover, the addition of phenformin eliminates resistance to antiangiogenic tyrosine kinase inhibitors (TKI), which prevent the uncontrolled metabolism of glucose in tumor cells. In this review, we evidence the great potential of phenformin as an anticancer agent. We thoroughly review its mechanism of action and clinical trial assays, specially focusing on current challenges and future perspectives of this promising drug.
YR 2019
FD 2019-07-05
LK http://hdl.handle.net/10668/14224
UL http://hdl.handle.net/10668/14224
LA en
DS RISalud
RD Apr 5, 2025