Figure 1.

A schematic diagram summarizing possible mechanisms underlying the risk associations of cancer with diabetes and the attenuating effects of statins, renin-angiotensin-system inhibitors (angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers), insulin and oral anti-diabetic drugs on cancer risk. Apart from obesity-associated insulin resistance, which can activate cell-signaling pathways such as the insulin-like growth factor-1 (IGF1) pathway to increase risk of cancer, hyperglycemia and dyslipidemia due to insufficient insulin action can activate angiotensin II, inflammatory and redox pathways that share multiple intracellular signals, including sterol regulatory element-binding proteins (SREBP), 3-hydroxy-3-methyl-glutaryl-CoA-reductase (HMGCR), adenosine monophosphate-activated protein kinase (AMPK) and nuclear factor kappa B (NF-KB) pathways to cause abnormal cell cycles to increase cancer risk. Treatment with RAS and HMGCR inhibitors together with correction of hyperglycemia including insulin, insulin sensitizers and insulin secretagogues can block these pathways at multiple sites to break the vicious cycles. ACEI, angiotensin-converting enzyme inhibitors; ARB, angiotensin II blockers; OAD, oral anti-diabetic drugs.