Cancer cachexia as a blueprint for treating obesity

Dissecting phenotypic features of cancer cachexia and studying their molecular underpinnings defines a strategy to identify therapeutic targets for the treatment of obesity.This ‘reverse engineering’ approach can, in principle, be applied to any type of pathology or extreme deviation from homeostasi...

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Bibliographic Details
Published in:Trends in endocrinology and metabolism 2023-07, Vol.34 (7), p.395-403
Main Authors: Jaschke, Nikolai P., Rachner, Tilman D.
Format: Article
Language:English
Subjects:
Cachexia - drug therapy
Cachexia - etiology
cancer cachexia
Humans
Neoplasms - complications
Neoplasms - metabolism
obesity
Obesity - metabolism
reverse engineering
systems biology
Weight Loss
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Summary:Dissecting phenotypic features of cancer cachexia and studying their molecular underpinnings defines a strategy to identify therapeutic targets for the treatment of obesity.This ‘reverse engineering’ approach can, in principle, be applied to any type of pathology or extreme deviation from homeostasis.First principle thinking is critical for successful application of reverse engineering.The most effective antiobesity drugs involve a central, satiety-inducing mechanism of action.Studying the neuronal circuits driving anorexia in cancer cachexia is likely of relevance for the development of innovative weight loss therapies. Effective pharmacological treatments to achieve significant and sustained weight loss in obese individuals remain limited. Here, we apply a ‘reverse engineering’ approach to cancer cachexia, an extreme form of dysregulated energy balance resulting in net catabolism. We discuss three phenotypic features of the disease, summarize the underlying molecular checkpoints, and explore their translation to obesity research. We then provide examples for established pharmaceuticals, which follow a reverse engineering logic, and propose additional targets that may be of relevance for future studies. Finally, we argue that approaching diseases from this perspective may prove useful as a generic strategy to fuel the development of innovative therapies.
ISSN:1043-2760
1879-3061
DOI:10.1016/j.tem.2023.04.001