Abstract
Insulin and IGFs play a significant role in cancer development and progression, including renal cell carcinoma (RCC). RCC is the most frequent type of kidney cancer in adults and the tenth most common malignancy worldwide. Insulin is normally associated with metabolism control, whereas IGFs are defined as proliferation regulators. Today, there is convincing evidence of an association between obesity and the risk of RCC. Indicated risk factors together with type 2 diabetes are irreversibly connected with circulating insulin and IGF levels. The interplay between these molecules, their receptors, and IGF-binding proteins might be crucial for RCC cell biology and RCC progression. Given the potent activity IGF/IGF receptor 1 (IGF1R) inhibitors demonstrate against RCC in basic research, some type of combination therapy may prove to be beneficial clinically in the management of RCC. This review addresses not only molecular but also clinical associations between insulin and IGF1 signaling pathways and both RCC biology and clinical course. Revealing these interactions may improve our understanding of basic molecular oncology processes in RCC and improve treatment strategies.
Highlights
Renal cell carcinoma (RCC), the incidence and mortality of which are rising at a rate of 2–3% per decade, is the tenth most common malignancy worldwide and the most frequent type of kidney cancer in adults
Similar, insulin and insulin-like growth factors (IGFs) act through similar receptors built as a tetrameric complex, characterized by two halves, which consist of an extracellular a-chain that is involved in ligand binding and an intracellular b-chain with functional tyrosine kinase (TK) domain
Many patients are presented with advanced RCC, which requires systematic treatment
Summary
Renal cell carcinoma (RCC), the incidence and mortality of which are rising at a rate of 2–3% per decade, is the tenth most common malignancy worldwide and the most frequent type of kidney cancer in adults. Recent advances in the molecular basis of RCC have allowed for a better understanding of the genetic disturbances that lead to renal carcinogenesis. Central to the biology of RCC is the loss of function of the von Hippel– Lindau (VHL) tumor suppressor gene, leading to the stabilization of hypoxia-inducible factors and inhibition of insulin-like growth factor receptor 1 (IGF1R) signaling (Datta 2000, Zhang et al 2013). We describe the role of insulin and insulin-like growth factors (IGFs) from both a clinical and a molecular point of view. Monitoring patient diabetic status or diet is an irreversible part of treatment, and a better understanding of its molecular background can improve patient outcome
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