Targeting obesity-related dysfunction in hormonally driven cancers

Abstract

Obesity is a risk factor for at least 13 different types of cancer, many of which are hormonally driven, and is associated with increased cancer incidence and morbidity. Adult obesity rates are steadily increasing and a subsequent increase in cancer burden is anticipated. Obesity-related dysfunction can contribute to cancer pathogenesis and treatment resistance through various mechanisms, including those mediated by insulin, leptin, adipokine, and aromatase signalling pathways, particularly in women. Furthermore, adiposity-related changes can influence tumour vascularity and inflammation in the tumour microenvironment, which can support tumour development and growth. Trials investigating non-pharmacological approaches to target the mechanisms driving obesity-mediated cancer pathogenesis are emerging and are necessary to better appreciate the interplay between malignancy, adiposity, diet and exercise. Diet, exercise and bariatric surgery are potential strategies to reverse the cancer-promoting effects of obesity; trials of these interventions should be conducted in a scientifically rigorous manner with dose escalation and appropriate selection of tumour phenotypes and have cancer-related clinical and mechanistic endpoints. We are only beginning to understand the mechanisms by which obesity effects cell signalling and systemic factors that contribute to oncogenesis. As the rates of obesity and cancer increase, we must promote the development of non-pharmacological lifestyle trials for the treatment and prevention of malignancy.

Inflammatory biomarkers and risk of breast cancer among young women in Latin America: a case-control study

“…Baseline data from a randomized controlled trial, in which premenopausal women with intraepithelial neoplasia or micro-invasive breast cancer were compared to healthy high-risk women (5-year Gail score > 1.3%), showed a decrease in risk with increasing adiponectin (but not leptin) concentrations [ 50 ]. Similar to what we observed for leptin, a borderline positive association with breast cancer risk was observed for small tumors only, which contrasts with the known anti-inflammatory properties of this adipokine [ 44 ].…”

“…In the present work, leptin was inversely associated with breast cancer risk in both univariate and fully adjusted model, however this association lost significance when the univariate model was adjusted for BMI. Leptin is a pro-inflammatory adipokine [ 44 ] strongly positively associated with BMI. Since we reported a strong inverse association between BMI and breast cancer in this population [ 6 ], the negative association between leptin and breast cancer may result from residual confounding.…”

Circulating Omentin-1 as a Biomarker at the Intersection of Postmenopausal Breast Cancer Occurrence and Cardiometabolic Risk: An Observational Cross-Sectional Study

“…More importantly, from a preventive perspective, circulating omentin-1 may increase through weight loss, physical exercise, and the adoption of a healthy diet such as the MedDiet which was found to be a positive predictor of serum omentin-1 in line with another study [ 68 , 69 ]. All three interventions, particularly the adoption of the MedDiet, are beneficial in the prevention of PBC, Mets, obesity, and CVD [ 7 , 70 , 71 , 72 ]. The majority of individuals presenting Mets are unaware of their condition and its repercussions [ 73 ].…”

Editorial: Metabolic Rewiring in Leukemias

“…These data provide further evidence of ROS directed metabolic changes in AML and the potential for metabolic targeting as novel therapeutic arm to combat this disease. Obesity increases the incidence and mortality of many cancers (13)(14)(15), including leukemia. In children with acute lymphoblastic leukemia (ALL), obesity increases relapse rate by ~50% (16,17) and risk of detectible minimal residual disease after the first month of chemotherapy more than two-fold (18).…”