Modeling the energetic cost of cancer as a result of altered energy metabolism: implications for cachexia
Tóm tắt
Cachexia affects most patients with incurable cancer. We hypothesize that in metastatic cancer the mass of the tumor as well as its level of anaerobic energy metabolism play a critical role in describing its energetic cost, which results in elevated resting energy expenditure and glucose utilization, leading to cachexia. Prior models of cancer cachexia may have underestimated the specific energetic cost of cancer as they have not taken the range of tumor mass and anaerobic energy metabolism fully into account. We therefore modelled the energetic cost of cancer as a function of the percentage of energy the cancer produces anaerobically, based on resting energy expenditure, glucose turnover, glucose recycling, and oxygen consumption in cancer patients found in previous studies. Data from two clinical studies where tumor burden was estimated and resting energy expenditure or oxygen consumption were measured lead to a broad range of estimates of tumor cost from 190 to 470 kcal/kg tumor/day. These values will vary based of the percentage of energy the cancer produces anaerobically (from 0 to 100 %), which in and of itself can alter the cost over a 2 to 3-fold range. In addition to the tumor cost/kg and the degree of anaerobic metabolism, the impact on a given individual patient will depend on tumor burden, which can exceed 1 kg in advanced metastatic disease. Considering these dimensions of tumor cost we are able to produce a 2-dimensional map of potential values, with an overall range of 100–1400 kcal/day. Quantifying the energetic cost of cancer may benefit an understanding of the tumor’s causation of cachexia. Our estimates of the range of tumor cost include values that are higher than prior estimates and suggest that in metastatic disease the tumor cost could be expected to eclipse attempts to stabilize energy balance through nutrition support or by drug therapies. Tumor mass and the percentage of anaerobic metabolism in the tumor contribute to the cost of the tumor on the body and potentially lead directly to negative energy balance and increased muscle wasting.
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