The prevalence of secondary neoplasms in acromegalic patients: possible preventive and/or protective role of metformin

Abstract

Background Acromegaly is a rare disease due to chronic growth hormone (GH) excess and the consequent increase in insulin-like growth factor-1 (IGF-1) levels. Both GH and IGF-1 play a role in intermediate metabolism affecting glucose homeostasis. The association between hyperinsulinemia/impaired glucose tolerance and an increased risk of cancer has been clarified. Insulin has a mitogenic effect through its interaction with the IGF-1 receptor (IGF-1R) that also binds IGF-1. On the other hand, metformin, an anti-hyperglycemic drug that decreases serum levels of insulin and IGF-1, could have a protective role in the treatment of endocrine tumors. Methods A retrospective, observational, multicenter study in 197 acromegalic patients, receiving/not receiving metformin, was performed to assess whether the prevalence of neoplasms might be correlated with insulin resistance and could eventually be modified by metformin treatment. Results In general, the occurrence of secondary neoplasia among our patients was significantly (pV = 0.035) associated with a positive family history of malignancy and with disease duration; a trend towards significance was observed in patients aged > 50 years. Acromegalic subjects who had undergone surgery showed a lower probability of developing a malignant tumor, whereas a higher prevalence of malignancies was observed in obese patients. No significant statistical difference was found when comparing metformin-treated or -untreated subjects for the presence of a second tumor. More interestingly, a trend towards statistical significance (pV = 0.065) was demonstrated in the metformin-treated group for the onset of a benign neoplasm. Conclusion Metformin could act directly on tumor cell metabolism and may have an adjuvant role in benign lesion progression.

Integrated or Independent Actions of Metformin in Target Tissues Underlying Its Current Use and New Possible Applications in the Endocrine and Metabolic Disorder Area

“…Recently, a retrospective, observational, multicenter study was performed to assess whether a metformin treatment might affect the prevalence of secondary neoplasms in acromegalic patients. No significant statistical difference was found between groups, when comparing metformin-treated to -untreated subjects for the presence of a second tumor [ 21 ]. On the other hand, a moderate preventive role of metformin on the onset of colon polyps in acromegaly, has been suggested by a distinct exploratory study [ 237 ], waiting for confirmation in a larger population.…”

“…These laboratory-based data have not been confirmed by clinical evidence yet. In fact, a few clinical observations may put the efficacy of metformin into doubt [ 21 , 22 ].…”

Insulin-like growth factor-1 signaling in the tumor microenvironment: Carcinogenesis, cancer drug resistance, and therapeutic potential

“…According to emerging evidence from molecular studies, the tumor microenvironment uses key paracrine factors such as insulin-like growth factor 1 (IGF-1) to fuel tumorigenesis (1)(2)(3). Certainly, in the current global obesity epidemic, IGFs have attracted attention for their potential role as a link between cancer and insulin resistance syndrome (4)(5)(6), a metabolic syndrome of increasing incidence that encompasses hyper/ hypoinsulinemia, hyper/hypoglycemia, dyslipidemia and hypertension, with a marked increase in risk to develop diabetes mellitus, cardiovascular diseases, and cancer (7)(8)(9)(10). Notably, recent reports show that antidiabetic drugs, such as metformin, can mediate anticancer effects partly by silencing IGF-1 expression (9,10).…”