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

Abstract

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.

Obesity and cancer: mechanistic insights from transdisciplinary studies

“…In addition to biologic mechanisms [reviewed in (Lashinger, et al 2014b)], non-biologic factors also contribute to reduced treatment efficacy in obese patients (Figure 2). There is considerable evidence to suggest that obese cancer patients are undertreated with systemic therapies (Lyman and Sparreboom 2013), and this may negatively impact cancer outcomes.…”

Obesity is an independent prognostic factor of decreased pathological complete response to neoadjuvant chemotherapy in breast cancer patients

“…Obesity is suggested to affect BC prognosis in a negative way [13]. This is secondary to the fact that obesity is associated with increasing serum leptin, insulin, estrogen hormones and other growth factors resulting in tumor size increase and metastatic cells stimulation which cause chemotherapy resistance [14]. It has been speculated that the chemotherapeutic agents may diffuse to lipid tissue at higher levels therefore reducing the amount of chemotherapeutics that need to circulate and diffuse into tumor tissue which may more commonly seen in obese patients.…”

Impact of obesity on chemotherapy management and outcomes in women with gynecologic malignancies

“…The obesity-associated metabolic conditions can lead to the conversion of monocytes to tumor-associated macrophages and the development of stem cell like properties. These factors are critical regulators of cell growth, neo-vascularity, inflammation, and proliferation of tumor initiating cells, all of which promote cancer development and progression [30,31], and may create the potential for the development of chemoresistance and poor responses to chemotherapy [31]. Obesity also may hamper surgery and make administration of radiotherapy quite challenging both of which can also impact clinical outcomes.…”