Phenformin as an Anticancer Agent: Challenges and Prospects

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 treat...

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Published in:International journal of molecular sciences 2019-07, Vol.20 (13), p.3316
Main Authors: García Rubiño, Mª Eugenia, Carrillo, Esmeralda, Ruiz Alcalá, Gloria, Domínguez-Martín, Alicia, A Marchal, Juan, Boulaiz, Houria
Format: Article
Language:English
Subjects:
Animals
Antineoplastic Agents - pharmacology
Breast cancer
Cancer
Chronic illnesses
Diabetes
Diabetes mellitus
Diabetes Mellitus, Type 2 - complications
Endoplasmic reticulum
Energy
Glucose
Growth factors
Hormones
Humans
Hyperglycemia
Hyperinsulinemia
Hypoxia
Insulin
Insulin resistance
Insulin-like growth factor I
Insulin-like growth factors
Kinases
Liver
Low concentrations
Metabolic syndrome
Models, Biological
Neoplasms - drug therapy
Obesity
Pancreas
Phenformin - chemistry
Phenformin - pharmacology
Phosphorylation
Physical fitness
Review
Risk
Risk Factors
Tamponade
Tumors
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms20133316