Endocrinology Unit, Department of Clinical and Experimental Medicine, University Magna Graecia of Catanzaro, Campus Universitario, località Germaneto, 88100 Catanzaro, Italy.
Endocr Relat Cancer. 2011 Jul 4;18(4):R125-47. doi: 10.1530/ERC-11-0074. Print 2011 Aug.
The widespread epidemic of obesity and type 2 diabetes has raised concern for the impact of these disorders as risk factors for cancer and has renewed the interest for studies regarding the involvement of hyperinsulinemia and insulin receptor (IR) in cancer progression. Overexpression of IR in cancer cells may explain their increased sensitivity to hyperinsulinemia. Moreover, IR isoform A (IR-A) together with autocrine production of its ligand IGF2 is emerging as an important mechanism of normal and cancer stem cell expansion and is a feature of several malignancies. De novo activation of the IR-A/IGF2 autocrine loop also represents a mechanism of resistance to anticancer therapies. Increasing knowledge of the IR role in cancer has important implications for cancer prevention, which should include control of insulin resistance and hyperinsulinemia in the population and meticulous evaluation of new antidiabetic drugs for their metabolic:mitogenic ratio. We are now aware that several anticancer treatments may induce or worsen insulin resistance that may limit therapy efficacy. Future anticancer therapies need to target the IR-A pathway in order to inhibit the tumor promoting effect of IR without impairing the metabolic effect of insulin.
肥胖症和 2 型糖尿病的广泛流行引起了人们对这些疾病作为癌症风险因素的影响的关注，并重新引发了对高胰岛素血症和胰岛素受体 (IR) 在癌症进展中作用的研究兴趣。癌细胞中 IR 的过度表达可以解释它们对高胰岛素血症的敏感性增加。此外，IR 同工型 A (IR-A) 与其配体 IGF2 的自分泌产生一起，正在成为正常和癌症干细胞扩增的重要机制，也是几种恶性肿瘤的特征。IR-A/IGF2 自分泌环的从头激活也是对癌症治疗产生耐药性的一种机制。IR 在癌症中的作用的不断增加对癌症预防具有重要意义，这应包括控制人群中的胰岛素抵抗和高胰岛素血症，并对新的抗糖尿病药物进行细致的代谢/促有丝分裂比评估。我们现在意识到，几种抗癌治疗可能会诱导或加重胰岛素抵抗，从而限制治疗效果。未来的抗癌疗法需要针对 IR-A 途径，以抑制 IR 的促肿瘤作用，而不损害胰岛素的代谢作用。
