The Role of Obesity in Renal Cell Carcinoma Patients: Clinical-Pathological Implications

Abstract

Obesity is a well-known risk factor for renal cell carcinoma (RCC) development. However, the RCC-obesity link has not been fully addressed when considering a comprehensive scenario starting from pathogenetic aspects through pathological issues up to the outcome of medical treatment. We therefore conducted an electronic PubMed search using keywords "obesity", "body mass index", "overweight", "renal cell carcinoma/kidney cancer", "medical treatment", "targeted therapy", and "immunotherapy/immune checkpoint inhibitors". The selected data supported a crosstalk between adipose tissue (adipocytes and other white adipose tissue cells) and cancer cells inducing several signaling pathways that finally stimulated angiogenesis, survival, and cellular proliferation. Accurate sampling of renal sinus fat correlated with a prognostic value. Retrospective clinical evidence in metastatic RCC patients with higher body mass index (BMI) and treated with targeted therapies and/or immune checkpoint inhibitors showed advantageous survival outcomes. Therefore, obesity may influence the course of RCC patients, although the interplay between obesity/BMI and RCC warrants a large prospective confirmation. We are therefore still far from determining a clear role of obesity as a prognostic/predictive factor in metastatic RCC patients undergoing targeted therapy and immunotherapy.

Keywords: body mass index; clinical outcomes; immunotherapy; obesity; renal cell carcinoma; targeted therapy.

Figure 1

Pathways show the influence of adipocytes on cancer. The substances released from adipocytes diffuse through the blood circulation and reach cancer cells, where they activate different cellular pathways leading to an increase of cell proliferation, survival, and angiogenesis. IGF1: insulin-like growth factor I. IGF1R: insulin-like growth factor 1 receptor. INSR: insulin receptor. IRS1: insulin receptor substrate 1. BAD: Bcl2-associated agonist of cell death. MAPK: mitogen-activated protein kinase. LEPR: leptin receptor. ADIPOR1: adiponectin receptor protein 1. ADIPOR2: adiponectin receptor protein 2. VEGFA: vascular endothelial growth factor A. AMPK: AMP-activated protein kinase. mTOR: serine/threonine-protein kinase mTOR. CP: ceruloplasmin. SLC31A1: high-affinity copper uptake protein 1. TNF: tumor necrosis factor. TNFRSF: tumor necrosis factor receptor superfamily. IL6: interleukin-6. IL6R: interleukin-6 receptor subunit alpha. PTGS2: prostaglandin G/H synthase 2. PI3K: phosphoinositide 3-kinases. AKT: serine/threonine kinase. HIF1A: hypoxia-inducible factor 1-alpha.

Figure 2

Proliferation of adipose tissue in renal sinus lipomatosis. Scale bar: 100 microns.