title: Pathogenesis of muscle wasting in cancer cachexia: targeted anabolic and anticatabolic therapies.
abstract: OBJECTIVE
  Cancer-related muscle loss, or cachexia, is the cause of death for approximately 2 million people worldwide and severely reduces quality of life. The degree of cachexia is inversely correlated with survival time; however, the exact mechanisms behind cancer-induced muscle wasting remain under investigation.
  
  
  RESULTS
  Cytokines such as tumor necrosis factor-alpha trigger degradatory pathways through nuclear factor-kappaB signaling that activate the ubiquitin-proteasome system and muscle proteolysis. Androgen treatment has been shown to reduce inflammatory cytokines and even stimulate anti-inflammatory cytokine production. Amino acid supplementation has been shown to induce muscle protein synthesis in ovarian cancer patients.
  
  
  CONCLUSIONS
  Targeted anabolic therapies aimed at preventing or reversing cancer cachexia might involve the combined use of androgens and amino acids working concurrently to enhance muscle protein synthesis and reduce muscle protein breakdown. Additional focused clinical studies are needed to identify muscle-specific targets or biomarkers for defined therapeutic approaches to slow or prevent cancer cachexia. In this review, we summarize the pathogenesis of cancer-related muscle wasting and discuss potential interventions at reversing or preventing cancer-related muscle loss.
authors.affiliation: Department of Internal Medicine, University of Texas Medical Branch, Galveston, Texas 77555-0460, USA.
authors.forename: Kimberlee
authors.initials: K
authors.lastname: Burckart
authors.forename: Sorin
authors.initials: S
authors.lastname: Beca
authors.forename: Randall J
authors.initials: RJ
authors.lastname: Urban
authors.forename: Melinda
authors.initials: M
authors.lastname: Sheffield-Moore
mesh_terms: D000596:Amino Acids / Q000627:therapeutic use*; D000728:Androgens / Q000627:therapeutic use*; D002100:Cachexia / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007249:Inflammation / Q000150:complications / Q000188:drug therapy* / Q000276:immunology; D009124:Muscle Proteins / Q000378:metabolism*; D009133:Muscular Atrophy / Q000188:drug therapy* / Q000209:etiology; D009369:Neoplasms / Q000150:complications*; D010051:Ovarian Neoplasms / Q000150:complications; D015398:Signal Transduction
chemical_list: D000596:Amino Acids; D000728:Androgens; D016207:Cytokines; D009124:Muscle Proteins
references.citation: J Physiol. 2006 Aug 15;575(Pt 1):305-15
references.pmid: 16777941
references.citation: Clin Nutr. 2007 Dec;26(6):736-43
references.pmid: 17804123
references.citation: J Clin Endocrinol Metab. 2004 Jul;89(7):3313-8
references.pmid: 15240608
references.citation: Am J Clin Nutr. 2006 Sep;84(3):623-32
references.pmid: 16960178
references.citation: J Natl Cancer Inst. 1996 Apr 17;88(8):550-2
references.pmid: 8606384
references.citation: Ann Surg Oncol. 2007 Feb;14(2):276-85
references.pmid: 17094025
references.citation: Exp Gerontol. 2006 Feb;41(2):215-9
references.pmid: 16310330
references.citation: Eur J Clin Invest. 2005 Mar;35(3):157-63
references.pmid: 15733069
references.citation: J Nutr. 1994 Jun;124(6):906-10
references.pmid: 7515956
references.citation: Nat Clin Pract Endocrinol Metab. 2006 Mar;2(3):146-59
references.pmid: 16932274
references.citation: Eur J Cancer. 2006 Jan;42(1):31-41
references.pmid: 16314085
references.citation: FASEB J. 2004 Jun;18(9):1025-7
references.pmid: 15084522
references.citation: Int J Cardiol. 2002 Sep;85(1):23-31
references.pmid: 12163207
references.citation: Biochem J. 1990 Feb 1;265(3):621-36
references.pmid: 1689567
references.citation: J Clin Endocrinol Metab. 2005 Mar;90(3):1453-9
references.pmid: 15598679
references.citation: Cell. 2004 Oct 15;119(2):285-98
references.pmid: 15479644
references.citation: J Biol Chem. 2003 Jan 24;278(4):2294-303
references.pmid: 12431991
references.citation: Curr Opin Clin Nutr Metab Care. 2009 Jan;12(1):72-7
references.pmid: 19057191
references.citation: Curr Opin Clin Nutr Metab Care. 2005 Jul;8(4):408-14
references.pmid: 15930966
references.citation: Biochem Biophys Res Commun. 2004 Jan 9;313(2):417-22
references.pmid: 14684178
references.citation: J Am Coll Surg. 2003 Jul;197(1):143-61
references.pmid: 12831935
references.citation: Int J Oncol. 2005 Sep;27(3):855-60
references.pmid: 16077938
references.citation: J Clin Endocrinol Metab. 2003 Jan;88(1):358-62
references.pmid: 12519877
references.citation: Am J Physiol Endocrinol Metab. 2004 Mar;286(3):E321-8
references.pmid: 14583440
references.citation: J Clin Endocrinol Metab. 1997 May;82(5):1332-7
references.pmid: 9141512
references.citation: Am J Clin Nutr. 2005 Nov;82(5):1065-73
references.pmid: 16280440
references.citation: Cancer Res. 1982 Jun;42(6):2495-8
references.pmid: 7074625
references.citation: CA Cancer J Clin. 2002 Mar-Apr;52(2):72-91
references.pmid: 11929007
references.citation: Am J Physiol Endocrinol Metab. 2003 May;284(5):E946-53
references.pmid: 12569085
references.citation: Am J Physiol Endocrinol Metab. 2005 Dec;289(6):E1007-14
references.pmid: 16030067
references.citation: Trends Endocrinol Metab. 2004 Apr;15(3):110-5
references.pmid: 15046739
references.citation: Eur J Cancer. 2000 Feb;36(3):289-92
references.pmid: 10708927
references.citation: Nutrition. 2005 Sep;21(9):977-85
references.pmid: 16043325
references.citation: Curr Opin Clin Nutr Metab Care. 2003 May;6(3):271-5
references.pmid: 12690258
references.citation: Physiol Rev. 2009 Apr;89(2):381-410
references.pmid: 19342610
references.citation: Oncol Rep. 2005 Jul;14(1):257-63
references.pmid: 15944798
references.citation: Nephrol Dial Transplant. 2001 Sep;16(9):1856-62
references.pmid: 11522870
references.citation: Am J Physiol. 1997 Jul;273(1 Pt 1):E99-107
references.pmid: 9252485
references.citation: J Biol Chem. 1999 Jan 8;274(2):787-94
references.pmid: 9873017
references.citation: Eur J Cardiovasc Prev Rehabil. 2008 Jun;15(3):293-9
references.pmid: 18525383
references.citation: Mol Cell Endocrinol. 2008 Sep 24;292(1-2):11-9
references.pmid: 18588941
references.citation: Urology. 2007 Jan;69(1):113-7
references.pmid: 17270630
references.citation: Essays Biochem. 2005;41:173-86
references.pmid: 16250905
references.citation: J Nutr. 2006 Jan;136(1 Suppl):314S-8S
references.pmid: 16365105
references.citation: Int J Biochem Cell Biol. 2005 Oct;37(10):1974-84
references.pmid: 16087388
references.citation: Clin Infect Dis. 1999 Mar;28(3):634-6
references.pmid: 10194091
references.citation: Cancer. 1986 Jul 1;58(1):183-6
references.pmid: 3518910
references.citation: J Mol Med (Berl). 2001 Jul;79(7):406-14
references.pmid: 11466563
references.citation: J Biol Chem. 1996 Oct 25;271(43):26690-7
references.pmid: 8900146
references.citation: FASEB J. 1998 Jul;12(10):871-80
references.pmid: 9657527
references.citation: Cell. 2004 Apr 30;117(3):399-412
references.pmid: 15109499
references.citation: Clin Exp Immunol. 1995 Oct;102(1):217-23
references.pmid: 7554393
references.citation: J Nutr. 2006 Jan;136(1 Suppl):227S-31S
references.pmid: 16365087
references.citation: J Clin Invest. 1993 Nov;92(5):2152-9
references.pmid: 8227330
references.citation: Am J Physiol Endocrinol Metab. 2006 Aug;291(2):E381-7
references.pmid: 16507602
references.citation: J Clin Endocrinol Metab. 1999 Aug;84(8):2705-11
references.pmid: 10443664
references.citation: Nutrition. 2001 Jan;17(1 Suppl):S1-20
references.pmid: 11428126
references.citation: Am J Clin Nutr. 2003 Aug;78(2):250-8
references.pmid: 12885705
references.citation: JAMA. 2000 Feb 9;283(6):763-70
references.pmid: 10683055
references.citation: Respir Res. 2001;2(5):269-72
references.pmid: 11686894
references.citation: J Clin Invest. 2004 Jan;113(1):115-23
references.pmid: 14702115
references.citation: Ageing Res Rev. 2009 Oct;8(4):251-67
references.pmid: 19716529
references.citation: Cell. 2004 Dec 29;119(7):907-10
references.pmid: 15620349
references.citation: Br Med Bull. 1999;55(1):181-95
references.pmid: 10695086
references.citation: Physiology (Bethesda). 2005 Oct;20:340-8
references.pmid: 16174873
references.citation: Ann Med. 2000 Apr;32(3):181-6
references.pmid: 10821325
references.citation: Med Hypotheses. 2007;69(2):310-21
references.pmid: 17376604
references.citation: Curr Opin Clin Nutr Metab Care. 2004 Jul;7(4):459-66
references.pmid: 15192450
references.citation: Crit Care Med. 2001 Oct;29(10):1936-42
references.pmid: 11588456
references.citation: J Am Soc Nephrol. 2003 Sep;14(9):2297-304
references.pmid: 12937306
references.citation: JAMA. 2001 Sep 12;286(10):1206-12
references.pmid: 11559266
references.citation: Am J Physiol. 1990 Oct;259(4 Pt 1):E477-82
references.pmid: 2221049
references.citation: J Clin Invest. 1998 May 1;101(9):2000-7
references.pmid: 9576765
references.citation: Am J Physiol. 1999 Sep;277(3):E513-20
references.pmid: 10484364
references.citation: Am J Physiol Cell Physiol. 2008 Oct;295(4):C986-93
references.pmid: 18701653
references.citation: J Nutr. 1999 Jan;129(1S Suppl):227S-237S
references.pmid: 9915905