Oncodiabetology I. Metabolic and molecular relationships between cancer and diabetes

In the recent decades, numerous studies have investigated the metabolic and molecular links between carbohydrate metabolic disorders and cancer, raising potential anti-tumor therapies. Based on epidemiological, preclinical, and clinical studies, now we know that advanced diabetes is a distinct risk factor of the development of many tumors, and even prediabetes may lead to the increased risk of developing cancer. Nowadays we can also state that the relationship is also present vice versa. It is a well-known fact that malignancies cause metabolic and molecular changes in the host over time resulting in an insulin-resistant state, characteristic of early diabetes. The tumor-induced insulin resistance may lead to the development of secondary diabetes in some patients with cancer. Furthermore, the diabetogenic ef-fect of the present anticancer therapies may worsen the metabolic condition. In recent years, research exploring the molecular causes of the correlation between malignancies and type 2 diabetes mellitus has highlighted the central role of RAS and PI3K signaling pathways. The altered function of these pathways significantly effects cell cycle, cellular metabolism, cell growth and proliferation, thus modifying cell survival, leading to tumorigenesis and tumor progres-sion and to insulin resistance as well. Without understanding the correlations between IGF receptors, RAS and PI3K signaling pathways the underlying molecular mechanism cannot be understood. Therefore, here we focus on these molecular mechanisms after a brief description of the most important metabolic connections between cancer and diabetes.