title: Endocrine side effects of anti-cancer drugs: effects of anti-cancer targeted therapies on lipid and glucose metabolism.
abstract: During the past years, targeted therapies for cancer have been developed using drugs that have significant metabolic consequences. Among them, the mammalian target of rapamycin (mTOR) inhibitors and, to a much lesser extent, the tyrosine kinase inhibitors (TKIs) are involved. mTOR plays a key role in the regulation of cell growth as well as lipid and glucose metabolism. Treatment with mTOR inhibitors is associated with a significant increase in plasma triglycerides and LDL cholesterol. mTOR inhibitors seem to increase plasma triglycerides by reducing the activity of the lipoprotein lipase which is in charge of the catabolism of triglyceride-rich lipoproteins. The increase in LDL cholesterol observed with mTOR inhibitors seems to be due to a decrease in LDL catabolism secondary to a reduction of LDL receptor expression. In addition, treatment with mTOR inhibitors is associated with a high incidence of hyperglycemia, ranging from 13 to 50% in the clinical trials. The mechanisms responsible for hyperglycemia with new onset diabetes are not clear, but are likely due to the combination of impaired insulin secretion and insulin resistance. TKIs do not induce hyperlipidemia but alter glucose homeostasis. Treatment with TKIs may be associated either with hyperglycemia or hypoglycemia. The molecular mechanism by which TKIs control glucose homeostasis remains unknown. Owing to the metabolic consequences of these agents used as targeted anti-cancer therapies, a specific and personalized follow-up of blood glucose and lipids is recommended when using mTOR inhibitors and of blood glucose when using TKIs.
authors.affiliation: Service Endocrinologie, Diabétologie et Maladies Métaboliques, INSERM CRI 866, Hôpital du Bocage, CHU Dijon, Université de Bourgogne, 21000 Dijon, France.
authors.forename: Bruno
authors.initials: B
authors.lastname: Vergès
authors.forename: Thomas
authors.initials: T
authors.lastname: Walter
authors.forename: Bertrand
authors.initials: B
authors.lastname: Cariou
mesh_terms: D000970:Antineoplastic Agents / Q000009:adverse effects*; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism*; D050260:Carbohydrate Metabolism / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000009:adverse effects; D006706:Homeostasis / Q000187:drug effects; D006801:Humans; D050356:Lipid Metabolism / Q000187:drug effects*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors*; D014280:Triglycerides / Q000097:blood
chemical_list: D000970:Antineoplastic Agents; D001786:Blood Glucose; D004791:Enzyme Inhibitors; D014280:Triglycerides; C546842:MTOR protein, human; D011505:Protein-Tyrosine Kinases; D058570:TOR Serine-Threonine Kinases