Understanding Metabolic Alterations in Cancer Cachexia through the Lens of Exercise Physiology

Abstract

Cancer cachexia is one of the leading causes of mortality for late-stage cancer patients. One of its key characteristics is abnormal metabolism and loss of metabolic flexibility, i.e., loss of ability to switch between use of fats and carbohydrates as needed. Here, it is hypothesized that late-stage systemic cancer creates a chronic resource drain on the body that may result in the same metabolic adaptations that occur during intense endurance exercise, activating some of the same mechanisms of nutrient consumption that are supposed to be transient during strenuous physical activity. This hypothesis is evaluated by creating a mathematical model that characterizes the relationships between increased exercise intensity and carbohydrate and fat oxidation. The model is parametrized using published data on these characteristics for a group of professional athletes, moderately active individuals, and individuals with metabolic syndrome. Transitions between different zones of relative nutrient consumption as a function of increased effort are captured through explicitly modeling ventilatory thresholds, particularly VT1 and VT2, where fat is primarily used below VT1, both carbohydrates and fats are used between VT1 and VT2, and where carbohydrates become the primary source of fuel above VT2. A simulation is conducted of projected patterns of nutrient consumption when simulated “effort” remains between VT1 and VT2, or above VT2, and it is proposed that it is the scenario when the simulated effort is maintained primarily above VT2 that most closely resembles metabolic patterns characteristic of cachexia. A discussion of a broader framework for understanding cachectic metabolism using insights from exercise physiology, including potential intervention strategies, concludes this paper.

Pattern discovery of long non‐coding RNAs associated with the herbal treatments in breast and prostate cancers

“…Furthermore, the top GO analysis indicated that the genes of lncRNA FUT8‐AS1 were mainly involved in the cellular carbohydrate biosynthetic process, leucine‐zipper, carbohydrate biosynthetic process, protein dimerization activity, and glucose metabolic process. FUT8‐AS1 is associated with mRNAs involved in the most frequently reported metabolic alterations in cancer patients, including resting energy expenditure linked with increased metabolism of carbohydrate, lipid, and protein metabolism, which are all typical of cancer cells [47,48]. Association of lncRNA FUT8‐AS1 to these mRNAs suggests that this lncRNA can serve as a novel biomarker or therapeutic target candidate for patients with BC or PC.…”