Oxidative stress and wasting in cancer.
OBJECTIVE
Cancer anorexia-cachexia syndrome is becoming a critical component in the comprehensive approach to cancer patients because it influences morbidity, mortality and quality of life. Consequently, pathogenic mechanisms have been elucidated to facilitate development of better therapies. Reported findings indicate that increased production of reactive oxygen species and reduced activity of antioxidant enzymes contribute to development of anorexia and cachexia in cancer.


RESULTS
Systemic inflammation impairs tryptophan handling, promoting oxidative stress, which appears to mimic hypothalamic negative feedback signalling. Thus, tryptophan contributes to cancer anorexia by stimulating hypothalamic serotonergic activity and promoting oxidative stress, because neuroinflammation facilitates tryptophan degradation into free radical generators via the kynurenine pathway. Upregulation of protein degradation by increased oxidative stress has been documented in cancer. Also, hypothalamic, cytokine-mediated suppression of fatty acid oxidation reduces food intake, and triggers mitochondrial biogenesis and oxidative gene expression in skeletal muscle, thus potentially increasing oxidative stress.


CONCLUSIONS
Increased oxidative stress contributes to cancer anorexia and cachexia. Preliminary clinical data on the efficacy of antioxidant therapy in cancer patients are encouraging, but uncertainty persists regarding the optimal dose and timing of administration. Also, better biological/genetic characterization of those cancer patients who are more likely to obtain significant clinical benefits appears necessary.
Laviano
Alessandro
A
Department of Clinical Medicine, University La Sapienza, Rome, Italy. alessandro.laviano@uniroma1.it
Meguid
Michael M
MM
Preziosa
Isabella
I
Rossi Fanelli
Filippo
F
D000855:Anorexia / Q000188:drug therapy / Q000209:etiology*; D000975:Antioxidants / Q000627:therapeutic use*; D002100:Cachexia / Q000188:drug therapy / Q000209:etiology*; D004734:Energy Metabolism; D006801:Humans; D009017:Morbidity; D009369:Neoplasms / Q000150:complications* / Q000378:metabolism; D018384:Oxidative Stress; D011788:Quality of Life; D017382:Reactive Oxygen Species; D013577:Syndrome; D014364:Tryptophan / Q000378:metabolism; D019282:Wasting Syndrome
D000975:Antioxidants; D017382:Reactive Oxygen Species; D014364:Tryptophan