Obesity and Resistance to Cancer Chemotherapy: Interacting Roles of Inflammation and Metabolic Dysregulation

The prevalence of obesity, an established risk factor for many chronic diseases, including several types of cancer, has risen steadily over the past four decades in the United States and worldwide. To date, research in this area has focused on the epidemiologic associations between obesity and cancer risk, as well as on the mechanisms underlying those associations. However, an emerging but understudied issue of clinical importance is the diminution of chemotherapeutic efficacy in obese cancer patients. The mechanisms underlying the negative impact of obesity on therapeutic responses are likely multifactorial. The effects of obesity on chemotherapy drug pharmacokinetics and dosage have been extensively reviewed elsewhere, so this review will focus on the interplay among obesity, increased inflammation, metabolic perturbations, and chemoresistance. The ultimate goal of this review is to delineate areas for future research that could lead to the identification of new targets and strategies for improved cancer outcomes in obese patients. Clinical Pharmacology & Therapeutics (2014); 96 4, 458–463. doi:10.1038/clpt.2014.136