Cited by 241Metabolism, Diabetes, and CancerCancer, Lipids, and MetabolismGrowth Hormone and Insulin-like Growth Factors

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Hyperinsulinaemia in cancer

Gallagher, Emily J., LeRoith, Derek·2020·Nature Reviews Cancer

DOI 10.1038/s41568-020-0295-5

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Abstract

Elevated circulating insulin levels are frequently observed in the setting of obesity and early type 2 diabetes, as a result of insensitivity of metabolic tissues to the effects of insulin. Higher levels of circulating insulin have been associated with increased cancer risk and progression in epidemiology studies. Elevated circulating insulin is believed to be a major factor linking obesity, diabetes and cancer. With the development of targeted cancer therapies, insulin signalling has emerged as a mechanism of therapeutic resistance. Although metabolic tissues become insensitive to insulin in the setting of obesity, a number of mechanisms allow cancer cells to maintain their ability to respond to insulin. Significant progress has been made in the past decade in understanding the insulin receptor and its signalling pathways in cancer, and a number of lessons have been learnt from therapeutic failures. These discoveries have led to numerous clinical trials that have aimed to reduce the levels of circulating insulin and to abrogate insulin signalling in cancer cells. With the rising prevalence of obesity and diabetes worldwide, and the realization that hyperinsulinaemia may contribute to therapeutic failures, it is essential to understand how insulin and insulin receptor signalling promote cancer progression.

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Authors: Gallagher, E. J., & LeRoith, D.
Affiliations: Tisch Cancer Institute (US)
Corresponding author: Gallagher, Emily J.
ORCID: Gallagher, Emily J.
LeRoith, Derek
Venue: Nature Reviews Cancer
Publisher: Springer Science and Business Media LLC
Published: 2020-09-09
Volume: 20
Issue: 11
Pages: 629-644
ISSN: 1474-175X (ISSN-L)
1474-1768
DOI: 10.1038/s41568-020-0295-5
OpenAlex: W3084040947
Cited by: 241
References: 201
Citations by year: 2026: 48 · 2025: 41 · 2024: 37 · 2023: 39 · 2022: 41 · 2021: 34 · 2020: 1
FWCI: 2.78
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature reviews. Cancer (publishedVersion)
PubMed (publishedVersion)
Funders: National Cancer Institute (K08CA190770)
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Growth Hormone and Insulin-like Growth Factors
Keywords: hyperinsulinemia, insulin receptor signaling, insulin resistance, obesity, type 2 diabetes, tumor progression, cancer therapy resistance, insulin receptor, tumor growth
MeSH terms: Diabetes Mellitus, Type 2, Humans, Hyperinsulinism, Insulin, Insulin Resistance, Neoplasms, Obesity, Receptor, Insulin, Signal Transduction, Antigens, CD, Comorbidity, Drug Resistance, Neoplasm

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