Is Host Metabolism the Missing Link to Improving Cancer Outcomes?

Abstract

For the past 100 years, oncologists have relentlessly pursued the destruction of tumor cells by surgical, chemotherapeutic or radiation oncological means. Consistent with this focus, treatment plans are typically based on key characteristics of the tumor itself such as disease site, histology and staging based on local, regional and systemic dissemination. Precision medicine is similarly built on the premise that detailed knowledge of molecular alterations of tumor cells themselves enables better and more effective tumor cell destruction. Recently, host factors within the tumor microenvironment including the vasculature and immune systems have been recognized as modifiers of disease progression and are being targeted for therapeutic gain. In this review, we argue that—to optimize the impact of old and new treatment options—we need to take account of an epidemic that occurs independently of—but has major impact on—the development and treatment of malignant diseases. This is the rapidly increasing number of patients with excess weight and its’ attendant metabolic consequences, commonly described as metabolic syndrome. It is well established that patients with altered metabolism manifesting as obesity, metabolic syndrome and chronic inflammation have an increased incidence of cancer. Here, we focus on evidence that these patients also respond differently to cancer therapy including radiation and provide a perspective how exercise, diet or pharmacological agents may be harnessed to improve therapeutic responses in this patient population.

Mitigation of Iron Irradiation-Induced Genotoxicity and Genomic Instability by Postexposure Dietary Restriction in Mice

“…To surmount this side effect, it needs to brace every nerve for a supreme effort. Multimodality treatments include not only therapeutic administration of radiation and pharmaceutical agents such as tissue-specific radiosensitizers and radioprotectors [ 11 , 119 – 121 ] but also prospective application of gene therapy (i.e., to modulate target gene splicing or aberrant splicing isoforms) [ 122 ], induction of hormesis and adaptive response [ 123 , 124 ], lifestyle intervention (including but not limited to such as dietary and nutritional interventions and administration of DR mimetic drugs) [ 114 , 125 , 126 ], psychiatric management [ 127 ], and other components such as public health issues. Among the treatments, dietary intervention as one of the adjuvant therapies is with a high acceptability and feasibility [ 128 ].…”

How Does Obesity Cause Cancer?

“…The articles accepted into this series focus on liver [ 4 , 5 , 6 ], uterine [ 7 ], skin [ 8 ], breast [ 9 , 10 , 11 ], prostate [ 12 ], colon [ 13 , 14 ], pancreatic [ 15 ], and acute lymphoblastic leukemia cancers [ 16 ], with a general overview of the potential impacts of obesity-related changes in host metabolism on cancer development and/or progression [ 17 ].…”

“…Finally, Wright and colleagues review the potential links between body mass, diet, and host metabolism to how well patients respond to anti-cancer treatment [ 17 ]. Together, these manuscripts help to us understand the complex relationship between excess body weight and cancer, and highlight idiosyncrasies in different types of cancer and model systems that may be useful in further dissecting the role of obesity and cancer incidence, progression, and/or sensitivity to treatment.…”