Type 2 Diabetes Mellitus and Cancer: The Role of Pharmacotherapy

Abstract

Type 2 diabetes mellitus (T2DM) is becoming increasingly prevalent worldwide. Epidemiologic data suggest that T2DM is associated with an increased incidence and mortality from many cancers. The purpose of this review is to discuss the links between diabetes and cancer, the effects of various antidiabetic medications on cancer incidence and mortality, and the effects of anticancer therapies on diabetes. DesignThis study is a review of preclinical and clinical data regarding the effects of antidiabetic medications on cancer incidence and mortality and the effects of anticancer therapies on glucose homeostasis. ResultsT2DM is associated with an increased risk and greater mortality from many cancer types. Metformin use has been associated with a decrease in cancer incidence and mortality, and there are many ongoing randomized trials investigating the effects of metformin on cancer-related outcomes. However, data regarding the association of other antidiabetes medications with cancer incidence and mortality are conflicting. Glucocorticoids, hormone-based therapies, inhibitors that target the phosphatidylinositol 3-kinase-Akt-mammalian target of rapamycin pathway, and insulin-like growth factor 1 receptor-targeted therapy have been associated with high rates of hyperglycemia. These agents mediate their deleterious metabolic effects by reducing insulin secretion and increasing insulin resistance in peripheral tissues. ConclusionStudies must be performed to optimize cancer screening strategies in individuals with T2DM. A greater understanding of the mechanisms that link diabetes and cancer are needed to identify targets for therapy in individuals with diabetes who develop cancer. Data from clinical studies are needed to further elucidate the effects of antidiabetic medications on cancer incidence and progression. As several anticancer therapies alter glucose homeostasis, physicians need to be aware of these potential effects. Careful patient screening and monitoring during treatment with these agents is necessary. J Clin Oncol 34:4261-4269. © 2016 by American Society of Clinical Oncology DIABETES MELLITUS AND CANCEREpidemiology Type 2 diabetes. Type 2 diabetes mellitus (T2DM) is a chronic progressive disease that is characterized by years of insulin resistance and hyperinsulinemia preceding the development of hyperglycemia. The prediabetes phase may predate the diagnosis of T2DM by up to 10 years. This potentially modifiable phase is frequently associated with the metabolic syndrome, a condition that comprises abdominal obesity, impaired glucose tolerance or impaired fasting glucose, dyslipidemia with elevated triglycerides (TGs) and low HDL cholesterol, and hypertension.1 The prevalence of T2DM and obesity has now reached epidemic proportions worldwide. A number of large-scale epidemiologic studies and meta-analyses, including a recent umbrella review of meta-analyses and observational studies, have shown a consistent increase in site-specific cancer incidence among patients with T2DM.2 This includes a two-to three-fol...

Colorectalis daganatokban a 2-es típusú cukorbetegség és a thrombocytosis előfordulása, a túlélésre gyakorolt hatásuk, a primer tumor műtéti eltávolítása előtt és után

“…Számos elmélet született, hogy e megfigyelés hátterében különböző, a T2DM-et befolyásoló, illetve a betegség miatt kialakuló tényezők állhatnak, mint például a hyperglykaemia, az inzulinrezisztencia, a hyperinsulinaemia, a magasabb széruminzu-lin-szerű növekedési faktor-1 (IGF1) koncentrációja, a folyamatos gyulladásos állapotok miatti magasabb citokinkoncentrációk, az oxidatív stressz, a dyslipidaemia vagy a fokozott thrombocytaaktiváció [20][21][22][23][24][25]. A T2DM-betegek kezelése során alkalmazott különböző antidiabetikumok tumorokkal szembeni védő-vagy ép-pen azok növekedését serkentő hatása jelenleg is számos klinikai gyógyszervizsgálat tárgyát képezi [21]. A legtöbb vizsgálat -a feltételezett tumorvédő hatása miatta metforminnal kapcsolatban folyt/folyik [26,27].…”

OP449 inhibits breast cancer growth without adverse metabolic effects

“…Targeted inhibitors for components of the IR signaling cascade have been the focus of many pre-clinical and clinical studies (Shlomai et al 2016). However, several of these agents, in particular inhibitors of the PI3K/Akt/mTOR pathway and IGF-1R-targeted therapies, have been associated with high rates of metabolic abnormalities in clinical trials (Shlomai et al 2016).…”

“…However, several of these agents, in particular inhibitors of the PI3K/Akt/mTOR pathway and IGF-1R-targeted therapies, have been associated with high rates of metabolic abnormalities in clinical trials (Shlomai et al 2016). We have previously shown that mTOR inhibition with rapamycin, significantly suppressed tumor growth in the presence of hyperinsulinemia, however it also markedly impaired glucose and lipid homeostasis and altered body composition (Fierz et al 2010).…”

“…While anti-neoplastic pharmacology has progressed immensely during the past decade, many anti-cancer drugs that target the insulin signaling pathway, including phosphoinositide-3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) inhibitors and the insulin-like growth factor 1 receptor (IGF-1R)-targeted therapies, have been associated in clinical trials with high rates of glycemic dysregulation and frank T2DM development (Shlomai, et al 2016). Therefore, there is an increasing need for effective, targeted anti-neoplastic agents that will maintain, or even improve the patients’ metabolic profiles.…”

Cancer, obesity, and diabetes: TKIs exert multiple effects on glucose homeostasis

“…Many of these agents target signalling pathways that influence cellular glucose metabolism, and increasing amounts of data demonstrate that TKI therapy can result in either elevated or decreased blood glucose levels, depending on the agent used and the clinical context 2,3 (TABLE 1). In some settings, hyperglycaemia has been reported as a common adverse effect of TKI therapy 4 .…”