Abstract
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.
Highlights
In 2011, it was estimated that one in three adults had obesity, which is, together with aging, one of the two main risk factors for the development of age-related diseases, such as cancer [1]
In order for type 1 insulin-like growth factor (IGF-1) to exert its mitogenic functions, it has to bind to its receptor (IGF-1R), which is present in tissues [21]
The results showed a greater association of metabolic syndrome with a series of cancers, such as colon–rectum, gastric, breast, liver, endometrium, pancreas, and bladder [4,25,26]
Summary
In 2011, it was estimated that one in three adults had obesity, which is, together with aging, one of the two main risk factors for the development of age-related diseases, such as cancer [1]. Various causes are common in both diseases, due to high levels of C-peptide [7], insulin resistance, hyperactivation of IGF-1 receptors due to the mitogenic effect of insulin [8], leptin, low adiponectin, and a pro-inflammatory environment [9] This association is argued by the fact that oral antidiabetics, such as phenformin and metformin, have therapeutic applications in various types of cancer. It is important to check the glycemic level in blood because an inadequate control of this is related to an increase in morbidity and mortality [11,12] Both diseases mainly have in common hyperinsulinemia, chronic inflammation, and endoplasmic reticulum stress, amongst other factors [12]. The risk of suffering from this disease decreases [12]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
