How Does Obesity Drive Human Carcinogenesis? Challenges in Dissecting the Mechanisms of Adipose-Epithelial Signaling

Abstract

Obesity is the second leading environmental association with cancer risk; yet, the mechanisms by which obesity drives carcinogenesis are poorly understood. The paper published in this issue of Cancer Prevention Research by Holowatyj and colleagues explores the mechanisms of human visceral adipose-epithelial signaling using samples collected at surgery in patients with invasive colorectal cancer. They identify pathway intermediates potentially involved in the regulation of fibrosis, inflammation, glycosis, and epithelial-mesenchymal transition in neoplastic tissue. 'Omics-based profiling of perioperative human biosamples has potential for inherent biases (preoperative and intraoperative drug therapies, hydration, dynamics, inflammatory response to surgical intervention) and appropriate control samples are difficult to identify and collect. Solutions to this dilemma may include strategies to identify patients undergoing similar surgical procedures but who are without neoplasms, for example, patients with gynecologic problems, abdominal exploration for suspected appendicitis, symptoms or resection of gall stone disease or undergoing bariatric surgery. As the field continues to grow, studies incorporating robust statistical analyses, validation of findings in diverse cohorts, and public data sharing will be essential to identify biological pathways linking obesity and carcinogenesis to be further interrogated using focused, hypothesis-driven approaches.See related article by Holowatyj et al., p. 817.