A weighty problem: metabolic perturbations and the obesity-cancer link

Abstract

Obesity is an established risk factor for several cancers, including breast, colon, endometrial, ovarian, gastric, pancreatic and liver, and is increasingly a public health concern. Obese cancer patients often have poorer prognoses, reduced response to standard treatments, and are more likely to develop metastatic disease than normo-weight individuals. Many of the pathologic features of obesity promote tumor growth, such as metabolic perturbations, hormonal and growth factor imbalances, and chronic inflammation. Although obesity exacerbates tumor development, the interconnected relationship between the two conditions presents opportunities for new treatment approaches, some of which may be more successful in obese cohorts. Here, we discuss the many ways in which excess adiposity can impact cancer development and progression and address potential preventive and therapeutic strategies to reduce the burden of obesity-related cancers.

Obstacles Posed by the Tumor Microenvironment to T cell Activity: A Case for Synergistic Therapies

“…Dividing cells require fatty acids (FA) to form new cell membrane lipid bilayers (O’Flanagan et al, 2015). Thus, it is not surprising that neoplasms also utilize free FA and lipogenesis following malignant transformation.…”

Tumor-linked HER2 expression: association with obesity and lipid-related microenvironment

“…However, regarding the pathogenesis of obesity-related cancers, a plausible explanation has been proposed [18], [19], [20]. The inflammatory situation in obesity perhaps creates a state of insulin resistance where cells cannot utilize glucose appropriately due to the defective response to insulin.…”

“…To overcome this condition, the pancreas produces more insulin, which causes hyperinsulinemia, alterations in IGF-binding proteins (IGFBPs), and increased biosynthesis of IGF-1 from the liver. Finally, in obesity, several biological components such as elevated bioavailable IGF-1, pro-inflammatory adipokines like leptin, and angiogenic factors like VEGF play a key role in the pathogenesis of cancer [18], [19], [20].…”

Obesity as a Promoter of Cancer Development and Progression

“…About 15-20% of all cancers are estimated to be caused by being obese or overweight [5,6]. Obese patients diagnosed with many types of cancers tend to have a worse prognosis, increased risk of metastatic cancers, and a shorter remission period than normal weight individuals [4,7]. However, some cancers are more strongly associated with obesity than others [4,7], and the correlation is dependent mainly on tissue type and patient cohort [5].…”