On our way to targeted therapy for cachexia in cancer?

Boddaert, M.; Gerritsen, Winald R.; Pinedo, H.M.

doi:10.1097/01.cco.0000228738.85626.ac

Cited by 26 publications

(25 citation statements)

References 44 publications

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“…To date, however, despite several years of co-ordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome [3]. Table 1 summarizes the currently available different therapeutic approaches, emerging drugs and future trends for the treatment of cancer-related anorexia-cachexia syndrome (CACS).…”

Section: Management Of Cancer Cachexiamentioning

confidence: 99%

Cancer cachexia: medical management

Mantovani

Madeddu

2009

Support Care Cancer

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To date, despite several years of co-ordinated efforts in basic and clinical research, practice guidelines for the prevention and treatment of cancer-related muscle wasting are lacking, mainly because of the multifactorial pathogenesis of the syndrome. From all the data presented, one can speculate that one single therapy may not be completely successful in the treatment of cachexia. From this point of view, treatments involving different combinations are more likely to be successful.

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Section: Management Of Cancer Cachexiamentioning

confidence: 99%

Cancer cachexia: medical management

Mantovani

Madeddu

2009

Support Care Cancer

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“…Present in up to 63% of all cancer patients (Laviano et al, 2005), as well as other chronic conditions including AIDS, heart failure, tuberculosis and renal failure (DeBoer and Marks, 2006), cachexia can significantly affect quality of life (Fearon et al, 2006) and response to therapy (Dewys et al, 1980). Current drug therapies include progestagens, anti-cytokine and anti-inflammatory drugs, and nutritional supplementation, but the efficacy of these approaches is limited at best (Boddaert et al, 2006). Illness-associated cachexia/anorexia involves problems with both energy intake and energy expenditure, in part mediated at the level of the central nervous system (CNS).…”

Section: Introductionmentioning

confidence: 99%

Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1β administration

Whitaker

Reyes

2008

Neuropharmacology

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SummaryLoss of appetite and cachexia is an obstacle in the treatment of chronic infection and cancer. Proinflammatory cytokines released from activated immune cells and acting in the central nervous system (CNS) are prime candidates for mediating these metabolic changes, potentially affecting both energy intake as well as energy expenditure. The effect of intravenous administration of two proinflammatory cytokines, IL-1β (15 µg/kg) and TNF-α(10 µg/kg) on food and water intake, locomotor activity, oxygen consumption (VO 2 ), and respiratory exchange ratio (RER) was evaluated. The two cytokines elicited a comparable decrease in food intake and activated similar numbers of cells in the paraventricular nucleus of the hypothalamus (PVH), a region that plays a critical role in the regulation of appetite and metabolism (determined via expression of the immediate early gene, c-fos). However, only IL-1β reduced locomotion and RER, and increased VO 2 , while TNF-α was without effect. To examine the role of the melanocortins in mediating IL-1β-induced metabolic changes, animals were pretreated centrally with a melanocortin receptor antagonist, HS014. Pretreatment with HS014 blocked the effect of IL-1β on food intake and RER at later time points (beyond 8hr post injection), as well as the hypoactivity and increased metabolic rate. Further, HS014 blocked the induction of Fos-ir in the PVH. These data highlight the importance of the melanocortin system, particularly within the PVH, in mediating a broad range of metabolic responses to IL-1β.

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“…© 2007 American Association for Cancer clincancerres.aacrjournals.org Downloaded from either short-term treatments for 2 weeks or longer treatments for 4 or 8 weeks have not been as effective in reducing significant weight loss (40). However, in a recent double-blind, placebo-controlled randomized trial done by Fearon et al (41) that involved more than 500 patients with either lung cancer or gastrointestinal cancers, a clinically relevant trend of weight gain was observed with a 2-g dose of eicosapentaenoic acid.…”

Section: Signaling Pathways and Clinical-translational Advancesmentioning

confidence: 99%

Cancer Cachexia Signaling Pathways Continue to Emerge Yet Much Still Points to the Proteasome

Acharyya

Guttridge

2007

Clinical Cancer Research

111

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Cachexia is a life-threatening consequence of cancer that diminishes both quality of life and survival. It is a syndrome that is characterized by extreme weight loss resulting mainly from the depletion of skeletal muscle. Research from the past decades investigating the mechanisms of tumor-induced muscle wasting has identified several key cachectic factors that act through the ubiquitin-dependent proteasome system. Signaling pathways that mediate the effects of these cachectic factors have also subsequently emerged. Here, we review some of these pathways specific to myostatin, nuclear factor nB, and the newly elucidated dystrophin glycoprotein complex. Although these molecules are likely to employ distinct modes of action, results suggest that they nevertheless maintain a link to the proteasome pathway. Therefore, although the proteasome remains a preferred choice for therapy, the continually emerging upstream signaling molecules serve as additional promising therapeutic targets for the treatment of tumor-induced muscle wasting.

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On our way to targeted therapy for cachexia in cancer?

Abstract: This review will focus on recent findings in relation to the molecular pathways leading to muscle wasting that have improved our current understanding of cachexia and will direct the future management of cachexia in cancer towards targeted therapies.

Cited by 26 publications

References 44 publications

Cancer cachexia: medical management

Cancer cachexia: medical management

Central blockade of melanocortin receptors attenuates the metabolic and locomotor responses to peripheral interleukin-1β administration

Cancer Cachexia Signaling Pathways Continue to Emerge Yet Much Still Points to the Proteasome

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