Insulin Resistance and Cancer: Epidemiology, Cellular and Molecular Mechanisms and Clinical Implications

Description

This book reviews the epidemiological associations between insulin resistance and cancer. This is followed by reviews of animal models which support this relationship and provide insight into potential mechanisms. Several chapters then provide detailed examination of the cellular and molecular changes characterizing the insulin resistant state, such as hyperinsulinemia, abnormal metabolism and hormone signaling, and how these interact with various tumor characteristics. For example some tumors present increased quantities of the fetal form of the insulin receptor, unique regulation of oxidative (Krebs’ cycle) metabolism (Warburg effect), as well as mutations in various relevant signaling pathways. Finally, the clinical implications of these data are integrated with considerations of insulin “sensitization” and potential metabolic interventions to prevent and treat cancer. It should be noted that while a number of cancers are associated with obesity the authors here have focused primarily on breast cancer as a key and significant model. Front Matter....Pages i-xi Insulin and the Physiology of Carbohydrate Metabolism....Pages 1-52 Insulin/IGF-1 Signaling Nodes and their Role in Carcinogenesis....Pages 53-76 The Mechanisms and Impact of Obesity and Insulin Resistance on Breast Cancer Incidence....Pages 77-99 Obesity and Cancer: Epidemiology....Pages 101-110 Insulin, Insulin Resistance, and Cancer Associations....Pages 111-140 Animal Models of Hyperinsulinemia, Insulin Resistance, and Cancer....Pages 141-157 Potential Mechanisms Linking Insulin to Cancer....Pages 159-180 Actions of Insulin As a Survival and Growth Factor: Akt, mTOR, and Regulation of Translation....Pages 181-192 AMP-Activated Protein Kinase and Cancer Cell Metabolism....Pages 193-211 The Role of the IGF Axis in Human Malignancy: Evidence from Epidemiological Studies and Tissue Analysis....Pages 213-242 IGF-I and Insulin Receptor Families in Cancer....Pages 243-268 Insulin Resistance: Clinical Implications for Cancer Treatment and Prevention....Pages 269-291 Back Matter....Pages 293-298