The double trouble of metabolic diseases: the diabetes–cancer link

The recent recognition of the clinical association between type 2 diabetes (T2D) and several types of human cancer has been further highlighted by reports of antidiabetic drugs treating or promoting cancer. At the cellular level, a plethora of molecules operating within distinct signaling pathways suggests cross-talk between the multiple pathways at the interface of the diabetes–cancer link. Additionally, a growing body of emerging evidence implicates homeostatic pathways that may become imbalanced during the pathogenesis of T2D or cancer or that become chronically deregulated by prolonged drug administration, leading to the development of cancer in diabetes and vice versa. This notion underscores the importance of combining clinical and basic mechanistic studies not only to unravel mechanisms of disease development but also to understand mechanisms of drug action. In turn, this may help the development of personalized strategies in which drug doses and administration durations are tailored to individual cases at different stages of the disease progression to achieve more efficacious treatments that undermine the diabetes–cancer association.