Phenformin as an Anticancer Agent: Challenges and Prospects

Autor: Esmeralda Carrillo, Mª Eugenia García Rubiño, Alicia Domínguez-Martín, Gloria Ruiz Alcalá, Houria Boulaiz, Juan A. Marchal
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
cancer stem cells
Biguanides
Review
Phenformin
Pharmacology
lcsh:Chemistry
chemistry.chemical_compound
0302 clinical medicine
Risk Factors
Neoplasms
Hyperinsulinemia
lcsh:QH301-705.5
Spectroscopy
Cancer
Biguanide
Cancer stem cells
General Medicine
Computer Science Applications
030220 oncology & carcinogenesis
Lactic acidosis
medicine.drug_class
Antineoplastic Agents
Hypoglycemia
Models
Biological
Catalysis
Inorganic Chemistry
03 medical and health sciences
Diabetes mellitus
medicine
Animals
Humans
cancer
Physical and Theoretical Chemistry
Molecular Biology
phenformin
PI3K/AKT/mTOR pathway
diabetes type 2
business.industry
Organic Chemistry
Type 2 Diabetes Mellitus
medicine.disease
030104 developmental biology
chemistry
Diabetes Mellitus
Type 2
lcsh:Biology (General)
lcsh:QD1-999
biguanides
business
Zdroj: International Journal of Molecular Sciences, Vol 20, Iss 13, p 3316 (2019)
Digibug. Repositorio Institucional de la Universidad de Granada
instname
International Journal of Molecular Sciences
ISSN: 1422-0067
Popis: 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.
This research was supported by the Fundación Mutua Madrileña (project FMM-AP16683-2017), Consejería de Salud Junta de Andalucía (PI-0089-2017), the MNat Scientitc Unit of Excellence (UCE.PP2017.0f) and the Chair “Doctors Galera-Requena in cancer stem cell research”.
Databáze: OpenAIRE
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