More than one decade ago, the International Association of Research on Cancer reported that obesity increases the risk in the development of several cancers. With the increasing epidemic rates that we face today, obesity is a major risk for cancer development. In fact, despite the increasing awareness of the public to cancer risk factors, the prevalence of several types of cancer remains high. Nevertheless, the mechanisms behind this association are not clear. Clinical and preclinical evidence indicate that obesity stands together with disturbed metabolism, insulin resistance, oxidative stress, chronic inflammation, abnormal presence of adipokines, growth factors and hormones, enhanced tissue fibrosis and imbalanced angiogenesis. Accordingly, obesity promotes a proinflammatory phenotype, characterized by a switch in M2 to M1 macrophages and exacerbated cytokine release, increased circulating levels of glucose, free fatty acids and hormones (namely insulin or leptin) and reduced circulating levels of adiponectin. All these features are often observed in neoplasia, suggesting a strong link between these two pathological conditions. This chapter highlights these putative mechanisms underlying the obesity-cancer interplay. We will tackle the processes that are imbalanced in obesity and can affect cancer development and progression, both at a systemic level as well as at local tumor environment. Identifying the features that characterize the obesity-associated cancer is mandatory for developing novel therapeutic strategies, which will definitely enhance quality of life and survival of these patients and reduce the concomitant economic burden of national healthcare systems.
Keywords: Adipocytokines, Adiposity, AMPK signaling, Angiogenesis, Cancer, Carbohydrate and lipid metabolism, Chemotherapy, Desmoplasia, Fibrosis, Glycemia, Host neighboring cell metabolism, Inflammation, Metabolic improvement therapeutic strategies, Metabolic organs adaptation, Oncology, Oxidative stress, Radiotherapy, Tumor metabolism, VEGF signaling.