Hyperinsulinaemia in cancer
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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Hyperinsulinaemia can contribute to certain obesity complications or related diseases, including hormonal disorders related to sex hormones and cancer.
“Hyperinsulinaemia, however, can contribute to certain obesity complications or related diseases, including hormonal disorders related to sex hormones and cancer (ie, mitogenic effect of insulin).98,99”
From Definition and diagnostic criteria of clinical obesity (2025) · cites this paper as [99]
Obesity is associated with increased risk for 13 types of cancer that account for more than 40% of cancer diagnoses annually.
“Obesity is associated with increased risk for 13 types of cancer that account for more than 40% of cancer diagnoses annually.99,133,134”
From Definition and diagnostic criteria of clinical obesity (2025) · cites this paper as [99]
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- Authors
- Gallagher, E. J., & LeRoith, D.
- Affiliations
- Tisch Cancer Institute (US)
- Corresponding author
- Gallagher, Emily J.
- Venue
- Nature Reviews Cancer
- Published
- 2020-09-09
- Volume
- 20
- Issue
- 11
- Pages
- 629-644
- ISSN
- 1474-175X (ISSN-L)
- 1474-1768
- 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
- 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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