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All in the family: Clueing into the link between metabolic syndrome and hematologic malignancies. Blood Rev 2015 Mar;29(2):71-80 PMID: 25433571

Pubmed ID

25433571

DOI

10.1016/j.blre.2014.09.010

Abstract

Metabolic syndrome constitutes a constellation of findings including central obesity, insulin resistance/type 2 diabetes mellitus (DM), dyslipidemia and hypertension. Metabolic syndrome affects 1 in 4 adults in the United States and is rapidly rising in prevalence, largely driven by the dramatic rise in obesity and insulin resistance/DM. Being central to the development of metabolic syndrome and its other related diseases, much focus has been placed on identifying the mitogenic effects of obesity and insulin resistance/DM as mechanistic clues of the link between metabolic syndrome and cancer. Pertinent mechanisms identified include altered lipid signaling, adipokine and inflammatory cytokine effects, and activation of PI3K/Akt/mTOR and RAS/RAF/MAPK/ERK pathways via dysregulated insulin/insulin-like growth factor-1 (IGF-1) signaling. Through variable activation of these multiple pathways, obesity and insulin resistance/DM pre-dispose to hematologic malignancies, imposing the aggressive and chemo-resistant phenotypes typically seen in cancer patients with underlying metabolic syndrome. Growing understanding of these pathways has identified druggable cancer targets, rationalizing the development and testing of agents like PI3K inhibitor idelalisib, mTOR inhibitors everolimus and temsirolimus, and IGF-1 receptor inhibitor linsitinib. It has also led to exploration of obesity and diabetes-directed therapies including statins and oral hypoglycemic for the management of metabolic syndrome-related hematologic neoplasms.

Author List

Karmali R, Dalovisio A, Borgia JA, Venugopal P, Kim BW, Grant-Szymanski K, Hari P, Lazarus H

Author

Parameswaran Hari MD Chief, Professor in the Medicine department at Medical College of Wisconsin




Scopus

2-s2.0-84932602551   10 Citations

MESH terms used to index this publication - Major topics in bold

Animals
Diabetes Mellitus, Type 2
Hematologic Neoplasms
Humans
Insulin Resistance
Lipid Metabolism
Metabolic Syndrome
Obesity
Signal Transduction
jenkins-FCD Prod-332 f92a19b0ec5e8e1eff783fac390ec127e367c2b5