The Influence of Exercise on the Insulin-like Growth Factor Axis in Oncology: Physiological Basis, Current, and Future Perspectives

Abstract

Exercise and physical activity have been shown to reduce the risk of many common cancers and strongly influence tumor biology. A cause-effect mechanism explaining this relationship is dependent on cellular pathways that can influence tumor growth and are exercise responsive. The insulin-like growth factor (IGF) axis is reported to promote the development and progression of carcinomas through cellular signaling in cancerous tissues. This review summarizes the physiologic basis of the role of the IGF axis in oncology and the influence of exercise on this process. We examined the effects of exercise prescription on the IGF axis in cancer survivors by evaluating the current scope of the literature.The current research demonstrates a remarkable heterogeneity and inconsistency in the responses of the IGF axis to exercise in breast, prostate, and colorectal cancer survivors. Finally, this review presents an in-depth exploration of the physiologic basis and mechanistic underpinnings of the seemingly disparate relationship between exercise and the IGF axis in oncology. Although there is currently insufficient evidence to categorize the effects of exercise prescription on the IGF axis in cancer survivors, the inconsistency of results suggests a multifaceted relationship, the complexities of which are considered in this review. Cancer Epidemiol Biomarkers Prev; 25(2);

Body size and composition, physical activity and sedentary time in relation to endogenous hormones in premenopausal and postmenopausal women: Findings from the UK Biobank

“…The effect sizes were, however, very small and after adjustment for BMI, only the association with sedentary time in premenopausal women remained significant. Likewise, many studies reported nonsignificant findings 14,36,41 although some found a positive association. 50 Overall, our study confirms that the associations of physical activity and sedentary time with the IGF-I concentration are negligible, particularly after adjustment for BMI.…”

“…Obesity and physical activity have been reported to influence circulating sex hormones and growth factors. [14][15][16][17] However, the evidence to date is not conclusive, particularly in premenopausal women due to small sample size as well as the cyclic nature of hormonal fluctuations before menopause. Given that the proliferative rate of mammary epithelial cells is highest in the mid-luteal phase, 18 menstrual cycle-specific analyses may provide insights into how obesity and physical activity influence the risk of premenopausal breast cancer.…”

Impact of cancer rehabilitation on the prognosis of patients with hepatocellular carcinoma

“…First, exercise may suppress the development and proliferation of HCC through modulation of insulin-like growth factor 1 signal. Insulin-like growth factor 1 concentration is related to an increase in tumor growth and development of colon cancer in in vivo and in vitro studies (40). Exercise improves insulin resistance and decreases levels of insulin-like growth factor 1 in patients with breast cancer (39).…”

The Adverse Effects of Androgen Deprivation Therapy in Prostate Cancer and the Benefits and Potential Anti-oncogenic Mechanisms of Progressive Resistance Training

“…Higher serum IGFBP-3 is associated with a lower risk of developing advanced-stage prostate cancer [53]. However, while PRT has been shown to reduce plasma IGF-1 [103] and increase IGFBP-3 [114] levels in prostate cancer, current epidemiological studies in cancer populations show significant heterogeneity in the response of the systemic IGF axis to exercise [118]. This discrepancy may be attributed to baseline concentrations of the IGF ligands, as Nishida et al [119] showed that participants with elevated baseline IGF-1 experienced the greatest decrease in response to exercise.…”

“…This discrepancy may be attributed to baseline concentrations of the IGF ligands, as Nishida et al [119] showed that participants with elevated baseline IGF-1 experienced the greatest decrease in response to exercise. Furthermore, there are current limitations in oncological research regarding the exercise response of autocrine, as compared to systemic IGF-1 [118]. In older adults with rheumatoid arthritis, PRT increased total lean and appendicular muscle mass, which was associated with increases in muscular IGF-1 and IGFBP-3 with no changes in systemic levels [120].…”