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Understanding the mechanisms and treatment options in cancer cachexia

Abstract

Cancer cachexia is a metabolic syndrome that can be present even in the absence of weight loss ('precachexia'). Cachexia is often compounded by pre-existing muscle loss, and is exacerbated by cancer therapy. Furthermore, cachexia is frequently obscured by obesity, leading to under-diagnosis and excess mortality. Muscle wasting (the signal event in cachexia) is associated not only with reduced quality of life, but also markedly increased toxicity from chemotherapy. Many of the primary events driving cachexia are likely mediated via the central nervous system and include inflammation-related anorexia and hypoanabolism or hypercatabolism. Treatment of cachexia should be initiated early. In addition to active management of secondary causes of anorexia (such as pain and nausea), therapy should target reduced food intake (nutritional support), inflammation-related metabolic change (anti-inflammatory drugs or nutrients) and reduced physical activity (resistance exercise). Advances in the understanding of the molecular biology of the brain, immune system and skeletal muscle have provided novel targets for the treatment of cachexia. The combination of therapies into a standard multimodal package coupled with the development of novel therapeutics promises a new era in supportive oncology whereby quality of life and tolerance to cancer therapy could be improved considerably.

Key Points

  • Cancer cachexia remains an important unmet medical need that affects patients' quality of life and treatment outcomes

  • Cachexia can be missed in an ever-increasingly obese population

  • Therapy should start early and can run in parallel with antineoplastic therapy

  • There is an urgent need to establish best supportive multimodal care for cachexia: beyond good clinical or oncological care, the treatable defects in dietary intake, physical activity and systemic inflammation should be addressed

  • Patients with cachexia should be actively considered for entry into clinical trials

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Figure 1: Dual contribution of metabolic change and reduced food intake to cachexia.
Figure 2: Extensive muscle wasting can be obscured by large fat mass.
Figure 3: Threshold definition for sarcopenia: a low level of muscle, characterized by a statistically significant increase in health risk.
Figure 4: Integration of fuel metabolism in the tumour-bearing state.
Figure 5: Muscle-cell proliferation and protein synthesis in response to growth factors and amino acids can be impaired by targeted cancer therapies.
Figure 6: Main targets for anticachexia treatments are those factors with an immediate effect on the development and aggravation of cachexia.

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References

  1. Fearon, K. et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 12, 489–495 (2011).

    Article  PubMed  Google Scholar 

  2. Arends, J. et al. ESPEN Guidelines on Enteral Nutrition: non-surgical oncology. Clin. Nutr. 25, 245–259 (2006).

    Article  CAS  PubMed  Google Scholar 

  3. Kubrak, C. et al. Nutrition impact symptoms: key determinants of reduced dietary intake, weight loss, and reduced functional capacity of patients with head and neck cancer before treatment. Head Neck 32, 290–300 (2010).

    PubMed  Google Scholar 

  4. Simons, J. P. et al. Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer: a randomized, placebo-controlled trial. Cancer 82, 553–560 (1998).

    Article  CAS  PubMed  Google Scholar 

  5. Nixon, D. W. et al. Hyperalimentation of the cancer patient with protein-calorie undernutrition. Cancer Res. 41, 2038–2045 (1981).

    CAS  PubMed  Google Scholar 

  6. Dodson, S. et al. Muscle wasting in cancer cachexia: clinical implications, diagnosis, and emerging treatment strategies. Annu. Rev. Med. 62, 265–279 (2011).

    Article  CAS  PubMed  Google Scholar 

  7. van Wetering, C. R. et al. Efficacy and costs of nutritional rehabilitation in muscle-wasted patients with chronic obstructive pulmonary disease in a community-based setting: a prespecified subgroup analysis of the INTERCOM trial. J. Am. Med. Dir. Assoc. 11, 179–187 (2010).

    Article  PubMed  Google Scholar 

  8. Barratt, S. M., Smith, R. C., Kee, A. J., Mather, L. E. & Cousins, M. J. Multimodal analgesia and intravenous nutrition preserves total body protein following major upper gastrointestinal surgery. Reg. Anesth. Pain Med. 27, 15–22 (2002).

    Article  PubMed  Google Scholar 

  9. Awad, S. et al. Marked changes in body composition following neoadjuvant chemotherapy for oesophagogastric cancer. Clin. Nutr. 31, 74–77 (2012).

    Article  PubMed  Google Scholar 

  10. Smith, M. R. et al. Changes in body composition during androgen deprivation therapy for prostate cancer. J. Clin. Endocrinol. Metab. 87, 599–603 (2002).

    Article  CAS  PubMed  Google Scholar 

  11. Antoun, S. et al. Association of skeletal muscle wasting with treatment with sorafenib in patients with advanced renal cell carcinoma: results from a placebo-controlled study. J. Clin. Oncol. 28, 1054–1060 (2010).

    Article  CAS  PubMed  Google Scholar 

  12. Helbekkmo, N. et al. Chemotherapy and quality of life in NSCLC PS 2 patients. Acta Oncol. 48, 1019–1025 (2009).

    Article  PubMed  Google Scholar 

  13. Kalantar-Zadeh, K. et al. Risk factor paradox in wasting diseases. Curr. Opin. Clin. Nutr. Metab. Care 10, 433–442 (2007).

    Article  PubMed  Google Scholar 

  14. McAuley, P. A. & Blair, S. N. Obesity paradoxes. J. Sports Sci. 29, 773–782 (2011).

    Article  PubMed  Google Scholar 

  15. Tan, B. H., Birdsell, L. A., Martin, L., Baracos, V. E. & Fearon, K. C. Sarcopenia in an overweight or obese patient is an adverse prognostic factor in pancreatic cancer. Clin. Cancer Res. 15, 6973–6979 (2009).

    Article  CAS  PubMed  Google Scholar 

  16. Prado, C. M. et al. Prevalence and clinical implications of sarcopenic obesity in patients with solid tumours of the respiratory and gastrointestinal tracts: a population-based study. Lancet Oncol. 9, 629–635 (2008).

    Article  PubMed  Google Scholar 

  17. Martin, L. et al. Prognostic factors in patients with advanced cancer: use of the patient-generated subjective global assessment in survival prediction. J. Clin. Oncol. 28, 4376–4383 (2010).

    Article  PubMed  Google Scholar 

  18. Pichard, C., Baracos, V. & Attaix, D. Would you buy a new tool to improve your practice? Curr. Opin. Clin. Nutr. Metab. Care 14, 221–222 (2011).

    Article  PubMed  Google Scholar 

  19. Lieffers, J. R. et al. A viscerally-driven cachexia syndrome in patients with advanced colorectal cancer: contributions of organ and tumor mass to whole body energy demands. Am. J. Clin. Nutr. 89, 1173–1179 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Stephens, N. A. et al. Sexual dimorphism modulates the impact of cancer cachexia on lower limb muscle mass and function. Clin. Nutr. 31, 499–505 (2012).

    Article  PubMed  Google Scholar 

  21. Costa, G. & Donaldson, S. S. Current concepts in cancer: effects of cancer and cancer treatment on the nutrition of the host. N. Engl. J. Med. 300, 1471–1474 (1979).

    Article  CAS  PubMed  Google Scholar 

  22. Andreyev, H. J., Norman, A. R., Oates, J. & Cunningham, D. Why do patients with weight loss have a worse outcome when undergoing chemotherapy for gastrointestinal malignancies? Eur. J. Cancer 34, 503–509 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Nitenberg, G. & Raynard, B. Nutritional support of the cancer patient: issues and dilemmas. Crit. Rev. Oncol. Hematol. 34, 137–168 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Stewart, G. D., Skipworth, R. J. & Fearon, K. C. Cancer cachexia and fatigue. Clin. Med. 6, 140–143 (2006).

    Article  Google Scholar 

  25. Watanabe, S. & Bruera, E. Anorexia and cachexia, asthenia, and lethargy. Hematol. Oncol. Clin. North Am. 10, 189–206 (1996).

    Article  CAS  PubMed  Google Scholar 

  26. Reid, J., McKenna, H., Fitzsimons, D. & McCance, T. Fighting over food: patient and family understanding of cancer cachexia. Oncol. Nurs. Forum 36, 439–445 (2009).

    Article  PubMed  Google Scholar 

  27. Dewys, W. D. et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Eastern Cooperative Oncology Group. Am. J. Med. 69, 491–497 (1980).

    Article  CAS  PubMed  Google Scholar 

  28. Ross, P. J. et al. Do patients with weight loss have a worse outcome when undergoing chemotherapy for lung cancer? Br. J. Cancer 90, 1905–1911 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Prado, C. M., Antoun, S., Sawyer, M. B. & Baracos, V. E. Two faces of drug therapy in cancer: drug-related lean tissue loss and its adverse consequences to survival and toxicity. Curr. Opin. Nutr. Metab. Care 14, 250–254 (2011).

    Article  CAS  Google Scholar 

  30. Mir, O. et al. Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS ONE 7, e37563 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Ardizzoni, A. et al. Cisplatin- versus carboplatin-based chemotherapy in first-line treatment of advanced non-small-cell lung cancer: an individual patient data meta-analysis. J. Natl Cancer Inst. 99, 847–857 (2007).

    Article  CAS  PubMed  Google Scholar 

  32. Straub, R. H., Cutolo, M., Buttgereit, F. & Pongratz, G. Energy regulation and neuroendocrine-immune control in chronic inflammatory diseases. J. Intern. Med. 267, 543–560 (2010).

    Article  CAS  PubMed  Google Scholar 

  33. Gibb, J., Audet, M. C., Hayley, S. & Anisman, H. Neurochemical and behavioral responses to inflammatory immune stressors. Front. Biosci. (Schol. Ed.) 1, 275–295 (2009).

    Article  Google Scholar 

  34. Myers, J. S. Proinflammatory cytokines and sickness behavior: implications for depression and cancer-related symptoms. Oncol. Nurs. Forum 35, 802–807 (2008).

    Article  PubMed  Google Scholar 

  35. Fearon, K. C., Glass, D. J. & Guttridge, D. C. Cancer cachexia: mediators, signaling, and metabolic pathways. Cell Metab. 16, 153–166 (2012).

    Article  CAS  PubMed  Google Scholar 

  36. Braun, T. P. et al. Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic-pituitary-adrenal axis. J. Exp. Med. 208, 2449–2463 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Tan, B. H. et al. P-selectin genotype is associated with the development of cancer cachexia. EMBO Mol. Med. 4, 462–471 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Das, S. K. et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333, 233–238 (2011).

    Article  CAS  PubMed  Google Scholar 

  39. Kortebein, P., Ferrando, A., Lombeida, J., Wolfe, R. & Evans, W. J. Effect of 10 days of bed rest on skeletal muscle in healthy older adults. JAMA 297, 1772–1774 (2007).

    Article  CAS  PubMed  Google Scholar 

  40. Ferrando, A. A., Stuart, C. A., Sheffield-Moore, M. & Wolfe, R. R. Inactivity amplifies the catabolic response of skeletal muscle to cortisol. J. Clin. Endocrinol. Metab. 84, 3515–3521 (1999).

    CAS  PubMed  Google Scholar 

  41. Murphy, R. A. et al. Aberrations in plasma phospholipid fatty acids in lung cancer patients. Lipids 47, 363–369 (2012).

    Article  CAS  PubMed  Google Scholar 

  42. Murphy, R. A. et al. Nutritional intervention with fish oil provides a benefit over standard of care for weight and skeletal muscle mass in patients with nonsmall cell lung cancer receiving chemotherapy. Cancer 117, 1775–1782 (2011).

    Article  CAS  PubMed  Google Scholar 

  43. Murphy, R. A. et al. Supplementation with fish oil increases first-line chemotherapy efficacy in patients with advanced nonsmall cell lung cancer. Cancer 117, 3774–3780 (2011).

    Article  CAS  PubMed  Google Scholar 

  44. Fakih, M. G. et al. Chemotherapy is linked to severe vitamin D deficiency in patients with colorectal cancer. Int. J. Colorectal Dis. 24, 219–224 (2009).

    Article  PubMed  Google Scholar 

  45. Zeisel, S. H. & da Costa, K. A. Choline: an essential nutrient for public health. Nutr. Rev. 67, 615–623 (2009).

    Article  PubMed  Google Scholar 

  46. Hasselgren, P. O. Glucocorticoids and muscle catabolism. Curr. Opin. Clin. Nutr. Metab. Care 2, 201–205 (1999).

    Article  CAS  PubMed  Google Scholar 

  47. Sheffield-Moore, M. et al. Androgen therapy induces muscle protein anabolism in older women. J. Clin. Endocrinol. Metab. 91, 3844–3849 (2006).

    Article  CAS  PubMed  Google Scholar 

  48. Gullett, N. P., Hebbar, G. & Ziegler, T. R. Update on clinical trials of growth factors and anabolic steroids in cachexia and wasting. Am. J. Clin. Nutr. 91, 1143S–1147S (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Bodine, S. C. et al. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nat. Cell Biol. 3, 1014–1019 (2001).

    Article  CAS  PubMed  Google Scholar 

  50. Glass, D. J. PI3 kinase regulation of skeletal muscle hypertrophy and atrophy. Curr. Top. Microbiol. Immunol. 346, 267–278 (2010).

    CAS  PubMed  Google Scholar 

  51. Trendelenburg, A. U. et al. Myostatin reduces Akt/TORC1/p70S6K signaling, inhibiting myoblast differentiation and myotube size. Am. J. Physiol. Cell Physiol. 296, C1258–1270 (2009).

    Article  CAS  PubMed  Google Scholar 

  52. Spiro, A., Baldwin, C., Patterson, A., Thomas, J. & Andreyev, H. J. The views and practice of oncologists towards nutritional support in patients receiving chemotherapy. Br. J. Cancer 95, 431–434 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Heyland, D. K. et al. Total parenteral nutrition in the surgical patient: a meta-analysis. Can. J. Surg. 44, 102–111 (2001).

    CAS  PubMed  Google Scholar 

  54. Jatoi, A., Kumar, S., Sloan, J. A. & Nguyen, P. L. On appetite and its loss. J. Clin. Oncol. 18, 2930–2932 (2000).

    Article  CAS  PubMed  Google Scholar 

  55. Ries, A. L. Pulmonary rehabilitation: summary of an evidence-based guideline. Respir. Care 53, 1203–1207 (2008).

    PubMed  Google Scholar 

  56. de Gramont, A. et al. The evolution of adjuvant therapy in the treatment of early-stage colon cancer. Clin. Colorectal Cancer 10, 218–226 (2011).

    Article  PubMed  Google Scholar 

  57. Vigano, A., Del Fabbro, E., Bruera, E. & Borod, E. The cachexia clinic: from staging to managing nutritional and functional problems in advanced cancer patients. Crit. Rev. Oncog. 17, 293–304 (2012).

    Article  PubMed  Google Scholar 

  58. Manini, T. M. Energy expenditure and aging. Ageing Res. Rev. 9, 1–11 (2010).

    Article  CAS  PubMed  Google Scholar 

  59. Moses, A. W., Slater, C., Preston, T., Barber, M. D. & Fearon, K. C. Reduced total energy expenditure and physical activity in cachectic patients with pancreatic cancer can be modulated by an energy and protein dense oral supplement enriched with n-3 fatty acids. Br. J. Cancer 90, 996–1002 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  60. Fearon, K. C. et al. Effect of a protein and energy dense N-3 fatty acid enriched oral supplement on loss of weight and lean tissue in cancer cachexia: a randomised double blind trial. Gut 52, 1479–1486 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Lundholm, K., Daneryd, P., Bosaeus, I., Korner, U. & Lindholm, E. Palliative nutritional intervention in addition to cyclooxygenase and erythropoietin treatment for patients with malignant disease: effects on survival, metabolism, and function. Cancer 100, 967–977 (2004).

    Article  CAS  Google Scholar 

  62. Baldwin, C., Spiro, A., Ahern, R. & Emery, P. W. Oral nutritional interventions in malnourished patients with cancer: a systematic review and meta-analysis. J. Natl Cancer Inst. 7, 371–385 (2012).

    Article  Google Scholar 

  63. Ferriolli, E. et al. Physical activity monitoring: a responsive and meaningful patient-centered outcome for surgery, chemotherapy, or radiotherapy? J. Pain Symptom Manage. 43, 1025–1035 (2012).

    Article  PubMed  Google Scholar 

  64. Lenk, K., Schuler, G. & Adams, V. Skeletal muscle wasting in cachexia and sarcopenia: molecular pathophysiology and impact of exercise training. J. Cachexia Sarcopenia Muscle 1, 9–21 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  65. Oldervoll, L. M. et al. Physical exercise for cancer patients with advanced disease: a randomized controlled trial. Oncologist 16, 1649–1657 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  66. Argilés, J. M., Busquets, S., López-Soriano, F. J., Costelli, P. & Penna, F. Are there any benefits of exercise training in cancer cachexia? J. Cachexia Sarcopenia Muscle 3, 73–76 (2012).

    Article  PubMed  PubMed Central  Google Scholar 

  67. Loprinzi, C. L. et al. Randomized comparison of megestrol acetate versus dexamethasone versus fluoxymesterone for the treatment of cancer anorexia/cachexia. J. Clin. Oncol. 17, 3299–3306 (1999).

    Article  CAS  PubMed  Google Scholar 

  68. Strasser, F. et al. Comparison of orally administered cannabis extract and δ-9-tetrahydrocannabinol in treating patients with cancer-related anorexia-cachexia syndrome: a multicenter, phase III, randomized, double-blind, placebo-controlled clinical trial from the Cannabis-In-Cachexia-Study-Group. J. Clin. Oncol. 24, 3394–3400 (2006).

    Article  CAS  PubMed  Google Scholar 

  69. Lundholm, K. et al. Anti-inflammatory treatment may prolong survival in undernourished patients with metastatic solid tumors. Cancer Res. 54, 5602–5606 (1994).

    CAS  PubMed  Google Scholar 

  70. Lundholm, K., Daneryd, P., Körner, U., Hyltander, A. & Bosaeus, I. Evidence that long-term COX-treatment improves energy homeostasis and body composition in cancer patients with progressive cachexia. Int. J. Oncol. 24, 505–512 (2004).

    CAS  PubMed  Google Scholar 

  71. Schmitz, G. & Ecker, J. The opposing effects of n-3 and n-6 fatty acids. Prog. Lipid Res. 47, 147–155 (2008).

    Article  CAS  PubMed  Google Scholar 

  72. Dewey, A., Baughan, C., Dean, T., Higgins, B. & Johnson, I. Eicosapentaenoic acid (EPA, an ω-3 fatty acid from fish oils) for the treatment of cancer cachexia. Cochrane Database of Systematic Reviews, Issue 1, Art. No.: CD004597. http://dx.doi.org/10.1002/14651858.CD004597.pub2.

  73. van der Meij, B. S. et al. Oral nutritional supplements containing (n-3) polyunsaturated fatty acids affect the nutritional status of patients with stage III non-small cell lung cancer during multimodality treatment. J. Nutr. 140, 1774–1780 (2010).

    Article  CAS  PubMed  Google Scholar 

  74. Noman, A. S. et al. Thalidomide inhibits lipopolysaccharide-induced tumor necrosis factor-α production via down-regulation of MyD88 expression. Innate Immun. 15, 33–41 (2009).

    Article  CAS  PubMed  Google Scholar 

  75. Bruera, E. et al. Thalidomide in patients with cachexia due to terminal cancer: preliminary report. Ann. Oncol. 10, 857–859 (1999).

    Article  CAS  PubMed  Google Scholar 

  76. Khan, Z. H. et al. Oesophageal cancer and cachexia: the effect of short-term treatment with thalidomide on weight loss and lean body mass. Aliment. Pharmacol. Ther. 17, 677–682 (2003).

    Article  CAS  PubMed  Google Scholar 

  77. Gordon, J. N. et al. Thalidomide in the treatment of cancer cachexia: a randomised placebo controlled trial. Gut 54, 540–545 (2005).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Moehler, T. Clinical experience with thalidomide and lenalidomide in multiple myeloma. Curr. Cancer Drug Targets 12, 372–390 (2012).

    Article  CAS  PubMed  Google Scholar 

  79. Heslin, M. J., Newman, E., Wolf, R. F., Pisters, P. W. & Brennan, M. F. Effect of systemic hyperinsulinemia in cancer patients. Cancer Res. 52, 3845–3850 (1992).

    CAS  PubMed  Google Scholar 

  80. Newman, E., Heslin, M. J., Wolf, R. F., Pisters, P. W. & Brennan, M. F. The effect of insulin on glucose and protein metabolism in the forearm of cancer patients. Surg. Oncol. 1, 257–267 (1992).

    Article  CAS  PubMed  Google Scholar 

  81. Lundholm, K. et al. Insulin treatment in cancer cachexia: effects on survival, metabolism, and physical functioning. Clin. Cancer Res. 13, 2699–2706 (2007).

    Article  CAS  PubMed  Google Scholar 

  82. Neary, N. M. et al. Ghrelin increases energy intake in cancer patients with impaired appetite: acute, randomized, placebo-controlled trial. J. Clin. Endocrinol. Metab. 89, 2832–2836 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Garcia, J. M., Friend, J. & Allen, S. Therapeutic potential of anamorelin, a novel, oral ghrelin mimetic, in patients with cancer-related cachexia: a multicenter, randomized, double-blind, crossover, pilot study. Support. Care Cancer http://dx.doi.org/10.1007/s00520-012-1500-1.

  84. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  85. Dalton, J. T. et al. The selective androgen receptor modulator GTx-024 (enobosarm) improves lean body mass and physical function in healthy elderly men and postmenopausal women: results of a double-blind, placebo-controlled phase II trial. J. Cachexia Sarcopenia Muscle 2, 153–161 (2011).

    Article  PubMed  PubMed Central  Google Scholar 

  86. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  87. Zaki, M. H., Nemeth, J. A. & Trikha, M. CNTO 328, a monoclonal antibody to IL-6, inhibits human tumor-induced cachexia in nude mice. Int. J. Cancer 111, 592–595 (2004).

    Article  CAS  PubMed  Google Scholar 

  88. Bayliss, T. J., Smith, J. T., Schuster, M., Dragnev, K. H. & Rigas, J. R. A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer. Expert Opin. Biol. Ther. 11, 1663–1668 (2011).

    Article  CAS  PubMed  Google Scholar 

  89. Prado, C. M. et al. Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma. Br. J. Cancer 106, 1583–1586 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. Han, H. Q. & Mitch, W. E. Targeting the myostatin signaling pathway to treat muscle wasting diseases. Curr. Opin. Support Palliat. Care 5, 334–341 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Zhou, X. et al. Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival. Cell 142, 531–543 (2010).

    Article  CAS  PubMed  Google Scholar 

  92. Benny Klimek, M. E. et al. Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia. Biochem. Biophys. Res. Commun. 391, 1548–1554 (2010).

    Article  CAS  PubMed  Google Scholar 

  93. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  94. US National Library of Medicine. ClinicalTrials.gov [online], (2012).

  95. American Dietetic Association. Oncology evidence-based nutrition practice guideline [online], (2007).

  96. August, D. A., Huhmann, M. B. & American Society for Parenteral and Enteral Nutrition (A. S. P. E. N.) Board of Directors. A. S. P. E. N. clinical guidelines: nutrition support therapy during adult anticancer treatment and in hematopoietic cell transplantation. JPEN J. Parenter. Enteral Nutr. 33, 472–500 (2009).

    Article  PubMed  Google Scholar 

  97. Bauer, J. D. et al. Evidence based practice guidelines for the nutritional management of cancer cachexia. Nutr. Dietetics 63 (Suppl. s2), S3–S32 (2006).

    Article  Google Scholar 

  98. Bozzetti, F. et al. ESPEN Guidelines on Parenteral Nutrition: non-surgical oncology. Clin. Nutr. 28, 445–454 (2009).

    Article  CAS  PubMed  Google Scholar 

  99. Moore, F. A., Ziegler, T. R., Heyland, D. K., Marik, P. E. & Bistrian, B. R. Developing research programs in clinical and translational nutrition. JPEN J. Parenter. Enteral. Nutr. 34 (Suppl. 6), 97S–105S (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  100. Commission on Cancer. Cancer Program Standards 2012: Ensuring Patient-Centered Care [online], (2012).

  101. OnkoZert [online], (2012).

  102. German Society of Hematology and Oncology [German, online], (2012).

  103. Boomsma, F. et al. Organisation of European Cancer Institutes Accreditation and Designation User Manual (eds Pierotti, M. A., van Harten W., Hummel, H. & Otter, R.) [online], (2011).

    Google Scholar 

  104. Council of Europe Committee of Ministers. Resolution ResAP (2003)3 on food and nutritional care in hospitals [online], (2003).

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All authors researched data for the article, made a substantial contribution to the discussion of the content, wrote the manuscript, and reviewed and edited it prior to submission.

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Correspondence to Kenneth Fearon.

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K. Fearon acts either a consultant for or receives honoraria or research support from Abbott, Alder Biopharmaceuticals, Nutricia and Novartis. J. Arends receives honoraria or research support from Abbott, Baxter, B. Braun, Fresenius-Kabi and Nutricia. V. Baracos declares no competing interests.

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Fearon, K., Arends, J. & Baracos, V. Understanding the mechanisms and treatment options in cancer cachexia. Nat Rev Clin Oncol 10, 90–99 (2013). https://doi.org/10.1038/nrclinonc.2012.209

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