The Insulin-Urothelial Axis: Evaluating Insulin Resistance as a Convergent Driver of Bladder Cancer Across Diverse Risk Factor Profiles.

Growing evidence suggests that insulin resistance (IR) might be a core, unifying mechanism linking various established risk factors for bladder cancer (BC). While factors like smoking, central obesity, sedentary lifestyle, and high-fat diets are known to increase BC risk, a common thread among them is their role in driving IR due to chronic hyperinsulinemia. Hyperinsulinemia promotes BC development in several ways. It acts as a potent growth factor, stimulating the proliferation and inhibiting the programmed cell death of malignant cells by activating the insulin/IGF signaling pathway. Furthermore, IR is closely associated with chronic low-grade inflammation and oxidative stress, both of which contribute to a pro-tumorigenic microenvironment. This convergence of growth-promoting and inflammatory signals highlights the central role of IR. While more research is needed to fully elucidate these complex interactions, the available data suggest that metabolic interventions aimed at improving insulin sensitivity could be a valuable, modifiable strategy for BC prevention.