Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Cachexia in cancer patients

Nature Reviews Cancer volume 2, pages 862–871 (2002)Cite this article

Key Points

Summary

  • Patients with cancer cachexia show a progressive loss of body weight, which is mainly due to loss of fat and skeletal muscle. Survival of cancer patients is directly related to the total weight loss and also the rate of weight loss.

  • Although anorexia occurs in cancer patients, the reduction in food intake alone is unable to explain the metabolic changes that are seen in cachexia. Nutritional supplementation and pharmacological manipulation of appetite are unable to restore loss of lean body mass.

  • Resting energy expenditure is increased in patients with lung and pancreatic cancer, but not in gastric and colorectal cancer. Increased energy expenditure might be related to the upregulation of uncoupling proteins (UCPs) — particularly UCP3 in skeletal muscle.

  • Loss of adipose tissue arises predominantly from an increase in lipolysis. Lipolysis is induced by a tumour product, lipid-mobilizing factor (LMF), which acts through a β3-adrenoceptor.

  • Loss of skeletal muscle arises from a fall in protein synthesis and an increase in protein degradation. The decreased protein synthesis could arise from the inactivity of the patient, coupled with a reduction in the supply or balance of amino acids due to acute-phase protein production. Increased protein degradation seems to be mainly due to an increased expression of the components of the ubiquitin-proteasome proteolytic pathway in skeletal muscle.

  • Tissue catabolism in cachexia is partially mediated by cytokines such as tumour necrosis factor-α (TNF-α) or interleukin (IL)-1 and IL-6. Tumour catabolic products such as LMF and proteolysis-inducing factor (PIF) directly stimulate tissue breakdown and are also correlated with human cancer cachexia.

  • Therapy has been mainly targeted at TNF-α and PIF. Agents that are directed solely at TNF-α have not shown clinical activity so far. Anticatabolic agents, such as eicosapentaenoic acid (EPA), effectively downregulate the increased expression of the ubiquitin-proteasome pathway in skeletal muscle and are clinically effective in restoring loss of lean body mass in cachectic cancer patients, especially in combination with a protein and energy-dense supplement.

  • Future therapy will consist of a combination of anabolic and anticatabolic agents.

Abstract

Cachexia — the massive (up to 80%) loss of both adipose tissue and skeletal muscle mass — is a significant factor in the poor performance status and high mortality rate of cancer patients. Although this metabolic defect has been known since cancer was first studied, it is only recently that major advances have been made in the identification of catabolic factors that act to destroy host tissues during the cachectic process. Although anorexia is frequently present, depression of food intake alone seems not to be responsible for the wasting of body tissues, as nutritional supplementation or pharmacological manipulation of appetite is unable to reverse the catabolic process — particularly with respect to skeletal muscle. However, recent clinical studies in cancer patients have shown that nutritional supplementation can be effective when combined with agents that attenuate the action of tumour factors and modifiers of the central effects on appetite might also show promise.

Access through your institution
Buy or subscribe

This is a preview of subscription content, access via your institution

Access options

Access through your institution

Buy this article

  • Purchase on SpringerLink
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Regulation of NPY production in the hypothalamic arcuate nucleus.
Figure 2: Cori cycle with sources of gluconeogenic substrates.
Figure 3: Synthesis and degradation of proteins in skeletal muscle.

Similar content being viewed by others

References

  1. DeWys, W. D. et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am. J. Med. 69, 491–497 (1980).

    CAS  PubMed  Google Scholar 

  2. Fearon, K. C. H. The mechanisms and treatment of weight loss in cancer. Proc. Nutr. Soc. 51, 251–265 (1992).

    CAS  PubMed  Google Scholar 

  3. Wigmore, S. J., Plester, C. E., Richardson, R. A. & Fearon, K. C. H. Changes in nutritional status associated with unresectable pancreatic cancer. Br. J. Cancer 75, 106–109 (1997).

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Kritchevsky, S. B. et al. Changes in plasma lipid and lipoprotein cholesterol and weight prior to diagnosis of cancer. Cancer Res. 51, 3198–3203 (1991).

    CAS  PubMed  Google Scholar 

  5. Grosvenor, M., Balcavage, L. & Chlebowski, R. T. Symptoms potentially influencing weight loss in a cancer population. Cancer 63, 330–338 (1989).

    CAS  PubMed  Google Scholar 

  6. Costa, G. et al. Weight loss and cachexia in lung cancer. Nutr. Cancer 2, 98–103 (1980).

    Google Scholar 

  7. Evans, W. K. et al. Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer. Cancer Res. 45, 3347–3353 (1985).

    CAS  PubMed  Google Scholar 

  8. Popiela, T., Lucchi, R. & Giongo, F. Methylprednisolone as palliative therapy for female terminal cancer patients. Eur. J. Cancer Clin. Oncol. 25, 1823–1829 (1989).

    CAS  PubMed  Google Scholar 

  9. Maltoni, M. et al. High-dose progestins for the treatment of cancer anorexia-cachexia syndrome. A systematic review of randomised clinical trials. Ann. Oncol. 12, 289–300 (2001).

    CAS  PubMed  Google Scholar 

  10. Loprinzi, C. L., Schaid, D. J., Dose, A. M., Burnham, N. L. & Jensen, M. D. Body-composition changes in patients who gain weight while receiving megestrol acetate. J. Clin. Oncol. 11, 152–154 (1993).

    CAS  PubMed  Google Scholar 

  11. Simons, J. P. F. H. A. et al. Effects of medroxyprogesterone acetate on food intake, body composition, and resting energy expenditure in patients with advanced, nonhormone-sensitive cancer. Cancer 82, 553–560 (1998).

    CAS  PubMed  Google Scholar 

  12. Rowland, K. M. Jr et al. Randomized double-blind placebo-controlled trial of cisplatin and etoposide plus megestrol acetate/placebo in extensive small-cell lung cancer: a North Central Cancer Treatment Group study. J. Clin. Oncol. 14, 135–141 (1996).

    CAS  PubMed  Google Scholar 

  13. Maltoni, M. et al. Medroxyprogesterone acetate reduces the in vitro production of cytokines and serotonin involved in anorexia/cachexia and emesis of peripheral blood mononuclear cells of cancer patients. Eur. J. Cancer 33, 602–607 (1997).

    Google Scholar 

  14. Bing, C., Taylor, S., Tisdale, M. J. & Williams, G. Cachexia in MAC16 adenocarcinoma: suppression of hunger despite normal regulation of leptin, insulin and hypothalamic neuropeptide Y. J. Neurochem. 79, 1004–1012 (2001).

    CAS  PubMed  Google Scholar 

  15. Marks, D. L., Ling, N. & Cone, R. D. Role of the central melanocortin system in cachexia. Cancer Res. 61, 1432–1438 (2001).Demonstrates that cachexia induced by lipopolysaccharide administration and by tumour growth is ameliorated by blockage of the hypothalamic melanocortin-4 receptor.

    CAS  PubMed  Google Scholar 

  16. Kardinal, C. G. et al. A controlled trial of cyproheptadine in cancer patients with anorexia and/or cachexia. Cancer 65, 2657–2661 (1990).

    CAS  PubMed  Google Scholar 

  17. Fredrix, E. W. H. M. et al. Energy balance in relation to cancer cachexia. Clin. Nutr. 9, 319–324 (1990).

    CAS  PubMed  Google Scholar 

  18. Falconer, J. S., Fearon, K. C. H., Plester, C. E., Ross, J. A. & Carter, D. C. Cytokines, the acute-phase response and resting energy expenditure in cachectic patients with pancreatic cancer. Ann. Surg. 219, 325–331 (1994).

    CAS  PubMed  PubMed Central  Google Scholar 

  19. McMillan, D. C. et al. Longitudinal study of body cell mass depletion and the inflammatory response in cancer patients. Nutr. Cancer 31, 101–105 (1998).

    CAS  PubMed  Google Scholar 

  20. Falconer, J. S. et al. Acute-phase protein response and survival duration of patients with pancreatic cancer. Cancer 75, 2077–2082 (1995).

    CAS  PubMed  Google Scholar 

  21. Clapham, J. C. et al. Mice overexpressing human uncoupling protein-3 in skeletal muscle are hyperphagic and lean. Nature 406, 415–418 (2000).

    CAS  PubMed  Google Scholar 

  22. Bing, C. et al. Increased gene expression of brown fat uncoupling protein (UCP)1 and skeletal muscle and UCP2 and UCP3 in MAC16-induced cancer cachexia. Cancer Res. 60, 2405–2410 (2000).

    CAS  PubMed  Google Scholar 

  23. Busquets, S. et al. Hyperlipemia: a role in regulating UCP3 gene expression in skeletal muscle during cancer cachexia? FEBS Lett. 505, 255–258 (2001).

    CAS  PubMed  Google Scholar 

  24. Collins, P., Bing, C., McCulloch, P. & Williams, G. Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans. Br. J. Cancer 86, 372–375 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  25. Busquets, S. et al. In the rat, tumor necrosis factor-α administration results in an increase in both UCP2 and UCP3 mRNA in skeletal muscle: a possible mechanism for cytokine-induced thermogenesis? FEBS Lett. 440, 348–350 (1998).

    CAS  PubMed  Google Scholar 

  26. Bing, C. et al. Expression of uncoupling proteins-1, -2 and-3 mRNA is induced by an adenocarcinoma-derived lipid-mobilizing factor. Br. J. Cancer 86, 612–618 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  27. Cabrero, A. et al. Down-regulation of uncoupling protein-3 and-2 by thiazolidinediones in C2C12 myotubes. FEBS Lett. 484, 37–42 (2000).

    CAS  PubMed  Google Scholar 

  28. Eden, E., Edstrom, S., Bennegard, K., Schersten, T. & Lundholm, K. Glucose flux in relation to energy expenditure in malnourished patients with and without cancer during periods of fasting and feeding. Cancer Res. 44, 1718–1724 (1984).

    CAS  PubMed  Google Scholar 

  29. Kaibara, A. et al. Leptin produces anorexia and weight loss without inducing an acute phase response or protein wasting. Am. J. Physiol. 274, R1518–R1525 (1998).

    CAS  PubMed  Google Scholar 

  30. Drott, C., Persson, H. & Lundholm, K. Cardiovascular and metabolic response to adrenaline infusion in weight-losing patients with and without cancer. Clin. Physiol. 9, 427–439 (1989).

    CAS  PubMed  Google Scholar 

  31. Hyltander, A., Daneryd, P., Sandstrom, R., Korner, U. & Lundholm, K. Beta-adrenoceptor activity and resting energy metabolism in weight losing cancer patients. Eur. J. Cancer 36, 330–334 (2000).

    CAS  PubMed  Google Scholar 

  32. Russell, S. T., Hirai, K. & Tisdale, M. J. Role of β3-adrenergic receptors in the action of a tumour lipid mobilizing factor. Br. J. Cancer 86, 424–428 (2002).

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Norton, J. A., Stein, T. P. & Brennan, M. F. Whole body protein synthesis and turnover in normal man and malnourished patients with and without cancer. Ann. Surg. 194, 123–128 (1981).

    CAS  PubMed  PubMed Central  Google Scholar 

  34. Lundholm, K., Bennegard, K., Eden, E. & Rennie, M. J. Efflux of 3-methylhistidine from the leg of cancer patients who experience weight loss. Cancer Res. 42, 4807–4811 (1982).

    CAS  PubMed  Google Scholar 

  35. Lundholm, K., Bylund, A. C., Holm, J. & Schersten, T. Skeletal muscle metabolism in patients with malignant tumour. Eur. J. Cancer 12, 465–473 (1976).

    CAS  PubMed  Google Scholar 

  36. Warren, R. S., Jeevanandam, M. & Brennan, M. F. Protein synthesis in the tumor-influenced hepatocyte. Surgery 98, 275–281 (1985).

    CAS  PubMed  Google Scholar 

  37. Lecker, S. V., Solomon, V., Mitch, W. E. & Goldberg, A. L. Muscle protein breakdown and critical role of the ubiquitin-proteasome pathway in normal and disease states. J. Nutr. 129, 227S–237S (1999).

    CAS  PubMed  Google Scholar 

  38. Goll, D. E., Thompson, V. F., Taylor, R. G. & Christiansen, J. A. Role of the calpain system in muscle growth. Biochimie 74, 225–237 (1992).

    CAS  PubMed  Google Scholar 

  39. Lowell, B. B., Ruderman, N. B. & Goodman, M. N. Evidence that lysosomes are not involved in the degradation of myofibrilar proteins in rat skeletal muscle. Biochem. J. 234, 237–240 (1986).

    CAS  PubMed  PubMed Central  Google Scholar 

  40. Hasselgren, P. O. & Fischer, J. E. Muscle cachexia: current concepts of intracellular mechanisms and molecular regulation. Ann. Surg. 233, 9–17 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  41. Jagoe, R. T., Redfern, C. P. F., Roberts, R. G., Gibson, G. J. & Goodship, T. H. J. Skeletal muscle mRNA levels for cathepsin B, but not components of the ubiquitin-proteasome pathway are increased in patients with lung cancer referred for thoracotomy. Clin. Sci. 102, 353–361 (2002).

    CAS  Google Scholar 

  42. Kisselev, A. F., Akopian, T. N., Castillo, V. & Goldberg, A. L. Proteasome active sites allosterically regulate each other, suggesting a cyclical bite-chew mechanism for protein breakdown. Mol. Cell 4, 395–402 (1999).

    CAS  PubMed  Google Scholar 

  43. Tanaka, K. Molecular biology of the proteasome. Biochem. Biophys. Res. Commun. 247, 537–541 (1998).

    CAS  PubMed  Google Scholar 

  44. Hasselgren, P.-O., Wray, C. & Mammen, J. Molecular regulation of muscle cachexia: it may be more than the proteasome. Biochem. Biophys. Res. Commun. 290, 1–10 (2002).

    CAS  PubMed  Google Scholar 

  45. Temparis, S. et al. Increasd ATP-ubiquitin-dependent proteolysis in skeletal muscle of tumor-bearing rats. Cancer Res. 54, 5568–5573 (1994).

    CAS  PubMed  Google Scholar 

  46. Lorite, M. J., Thompson, M. G., Drake, J. L., Carling, G. & Tisdale, M. J. Mechanism of muscle protein degradation induced by a cancer cachectic factor. Br. J. Cancer 78, 850–856 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  47. Bodine, S. C. et al. Identification of ubiquitin ligases required for skeletal muscle atrophy. Science 294, 1704–1708 (2001).

    CAS  PubMed  Google Scholar 

  48. Gomes, M. D., Lecker, S. H., Jagoe, R. T., Navon, A. & Goldberg, A. L. Atrogin-1, a muscle specific F-box protein highly expressed during muscle atrophy. Proc. Natl Acad. Sci. USA 98, 14440–14445 (2001).References 47 and 48 provide evidence that ubiquitin-protein ligases (E3) might be rate-limiting for proteasome proteolysis in skeletal muscle.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Bossola, M. et al. Increased muscle ubiquitin mRNA levels in gastric cancer . Am J Physiol Regul Integr Comp Physiol 280, R1518–R1523 (2001).

    CAS  PubMed  Google Scholar 

  50. Williams, A., Sun, X., Fischer, J. E. & Hasselgren, P.-O. The expression of genes in the ubiquitin-proteasome proteolytic pathway is increased in skeletal muscle from patients with cancer. Surgery 126, 744–750 (1999).The first report of increased expression of genes in the ubiquitin-proteasome proteolytic pathway in muscle tissue from patients with cancer.

    CAS  PubMed  Google Scholar 

  51. Mahony, S. M. & Tisdale, M. J. Induction of weight loss and metabolic alterations by human recombinant tumour necrosis factor. Br. J. Cancer 58, 345–351 (1988).

    CAS  PubMed  PubMed Central  Google Scholar 

  52. Strassman, G., Fong, M., Kenney, J. S. & Jacob, C. O. Evidence for the involvement of IL-6 in experimental cancer cachexia. J. Clin. Invest. 89, 1681–1684 (1992).

    Google Scholar 

  53. Espat, N. J. et al. Ciliary neurotrophic factor is catabolic and shares with IL-6 the capacity to induce an acute phase response. Am. J. Physiol. 271, R185–R190 (1996).

    CAS  PubMed  Google Scholar 

  54. Langstein, H. et al. The role of γ-interferon and tumor necrosis factor-α in an experimental rat model of cancer cachexia. Cancer Res. 51, 2302–2306 (1991).

    CAS  PubMed  Google Scholar 

  55. Hirai, K., Hussey, H. J., Barber, M. D., Price, S. A. & Tisdale, M. J. Biological evaluation of a lipid-mobilizing factor isolated from the urine of cancer patients. Cancer Res. 58, 2359–2365 (1998).

    CAS  PubMed  Google Scholar 

  56. Todorov, P. et al. Characterization of a cancer cachectic factor. Nature 379, 739–742 (1996).This is the first report on the isolation and characterization of a 24-kDa glycoprotein that is produced by cachexia-inducing mouse and human tumours, which initiates protein catabolism in skeletal muscle.

    CAS  PubMed  Google Scholar 

  57. Oliff, A. et al. Tumors secreting human TNF/cachectin induce cachexia in mice. Cell 50, 555–561 (1987).

    CAS  PubMed  Google Scholar 

  58. Strassmann, G. et al. Mechanisms of experimental cancer cachexia. Local involvement of IL-1 in colon-26 tumor. J. Immunol. 150, 2341–2346 (1993).

    CAS  PubMed  Google Scholar 

  59. Henderson, J. T., Mullen, B. J. M. & Roder, J. C. Physiological effects of CNTF-induced wasting. Cytokine 8, 784–793 (1996).

    CAS  PubMed  Google Scholar 

  60. Matthys, P. et al. Anti-interferon-γ antibody treatment, growth of Lewis lung tumours in mice and tumour-associated cachexia. Eur. J. Cancer 27, 182–186 (1991).

    CAS  PubMed  Google Scholar 

  61. Beck, S. A. & Tisdale, M. J. Production of lipolytic and proteolytic factors by a murine tumor-producing cachexia in the host. Cancer Res. 47, 5919–5923 (1987).

    CAS  PubMed  Google Scholar 

  62. Karayiannakis, A. J. et al. Serum levels of tumor necrosis factor-α and nutritional status in pancreatic cancer patients. Anticancer Res. 21, 1355–1358 (2001).

    CAS  PubMed  Google Scholar 

  63. Maltoni, M. et al. Serum levels of tumour necrosis factor and other cytokines do not correlate with weight loss and anorexia in cancer patients. Support. Care Cancer 5, 130–135 (1997).

    CAS  PubMed  Google Scholar 

  64. Scott, H. R., McMillan, D. C., Crilly, A., McArdle, C. S. & Milroy, R. The relationship between weight loss and interleukin-6 in non-small-cell lung cancer. Br. J. Cancer 73, 1560–1562 (1996).Provides evidence of increased IL-6 in weight-losing cancer patients that might be related to weight loss and the APR.

    CAS  PubMed  PubMed Central  Google Scholar 

  65. Moradi, M. M. et al. Serum and ascitic fluid levels of interleukin-1, interleukin-6 and tumor necrosis factor-alpha in patients with ovarian epithelial cancer. Cancer 72, 2433–2437 (1993).

    CAS  PubMed  Google Scholar 

  66. Lorite, M. J. et al. Activation of ATP-ubiquitin-dependent proteolysis in skeletal muscle in vivo and murine myoblasts in vitro by a proteolysis-inducing factor (PIF). Br. J. Cancer 85, 297–302 (2001).

    CAS  PubMed  PubMed Central  Google Scholar 

  67. Wigmore, S. J. et al. Characteristics of patients with pancreatic cancer expressing a novel cancer cachectic factor. Br. J. Surg. 87, 53–58 (2000).

    CAS  PubMed  Google Scholar 

  68. Hauner, H., Petruschke, T., Russ, M., Rohrig, K. & Eckel, J. Effects of tumor necrosis factor alpha (TNFα) on glucose transport and lipid metabolism of newly-differentiated human fat cells in cell culture. Diabetologica 38, 764–771 (1995).

    CAS  Google Scholar 

  69. Li, Y. P. et al. Skeletal muscle myocytes undergo protein loss and reactive oxygen-mediated NF-κB activation in response to tumor necrosis factor α. FASEB J. 12, 871–880 (1998).Demonstrates that TNF-α is capable of directly inducing protein degradation in vitro through the ubiquitin-proteasome pathway.

    CAS  PubMed  Google Scholar 

  70. Ebisui, C. et al. Interleukin-6 induces proteolysis by activating intracellular proteases (cathepsins B and L, proteasome) in C2C12 myotubes. Clin. Sci. 89, 431–439 (1995).

    CAS  Google Scholar 

  71. Llovera, M. et al. Different cytokines modulate ubiquitin gene expression in rat skeletal muscle. Cancer Lett. 133, 83–87 (1998).

    CAS  PubMed  Google Scholar 

  72. Watchorn, T. M., Waddell, I. D., Dowidar, N. & Ross, J. A. Proteolysis-inducing factor regulates hepatic gene expression via the transcription factors NF-κB and STAT3. FASEB J. 15, 562–564 (2001).Suggests that PIF, in addition to inducing protein degradation in skeletal muscle, might be responsible for APP production in liver via activation of cytokine production.

    CAS  PubMed  Google Scholar 

  73. Cangiano, C. et al. Effects of administration of oral branched-chain amino acids on anorexia and caloric intake in cancer patients. J. Natl Cancer Inst. 88, 550–552 (1996).

    CAS  PubMed  Google Scholar 

  74. Lissoni, P. et al. Is there a role for melatonin in the treatment of neoplastic cachexia? Eur. J. Cancer 32A, 1340–1343 (1996).

    CAS  PubMed  Google Scholar 

  75. Lissoni, P. et al. Inhibition of tumor necrosis factor-alpha secretion by pentoxifylline in advanced cancer patients with abnormally high blood levels of tumor necrosis factor α J. Biol. Regul. Homeost. Agents 7, 73–75(1993).

    CAS  PubMed  Google Scholar 

  76. Goldberg, R. M. et al. Pentoxifylline for treatment of cancer anorexia and cachexia? A randomised, double-blind, placebo-controlled trial. J. Clin. Oncol. 13, 2856–2859 (1995).

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  78. Reyes-Teran, G. et al. Effects of thalidomide on HIV-associated wasting syndrome: a randomized, double-blind, placebo-controlled trial. AIDS 10, 1501–1507 (1996).

    CAS  PubMed  Google Scholar 

  79. McMillam, D. C., Gorman, P. O., Fearon, K. C. H. & McArdle, C. S. A pilot study of megestrol acetate and ibuprofen in the treatment of cachexia in gastrointestinal patients. Br. J. Cancer 76, 788–790 (1997).

    Google Scholar 

  80. Whitehouse, A. S., Smith, H. J., Drake, J. L. & Tisdale, M. J. Mechanism of attenuation of skeletal muscle protein catabolism in cancer cachexia by eicosapentaenoic acid. Cancer Res. 61, 3604–3609 (2001).Provides a mechanistic interpretation of the effect of EPA on protein degradation in skeletal muscle by downregulating the increased expression of the ubiquitin-proteasome proteolytic pathway that accompanies cachexia.

    CAS  PubMed  Google Scholar 

  81. Wigmore, S. J. et al. The effect of polyunsaturated fatty acids on the progress of cachexia in patients with pancreatic cancer. Nutrition 12, S27–S30 (1996).

    CAS  PubMed  Google Scholar 

  82. Wigmore, S. J., Barber, M. D., Ross, J. A., Tisdale, M. J. & Fearon, K. C. H. Effect of oral eicosapentaenoic acid on weight loss in patients with pancreatic cancer. Nutr. Cancer 36, 177–184 (2000).

    CAS  PubMed  Google Scholar 

  83. Barber, M. D., Ross, J. A., Voss, A. C., Tisdale, M. J. & Fearon, K. C. H. The effect of an oral nutritional supplement enriched with fish oil on weight-loss in patients with pancreatic cancer. Br. J. Cancer 81, 80–86 (1999).Combination of fish oil with an energy-dense nutritional supplement was found to increase body weight in cachectic cancer patients. The increase in body weight was solely due to an increase in lean body mass.

    CAS  PubMed  PubMed Central  Google Scholar 

  84. May, P. E., Barker, A., D'Olimpio, J. T., Hourihane, A. & Abumrad, N. N. Reversal of cancer-related wasting using oral supplementation with a combination of β-hydroxy-β-methylbutyrate, arginine and glutamine. Am. J. Surg. 183, 471–479 (2002).This is the first clinical trial demonstrating the ability of the leucine metabolite, β-hydroxy-β-methylbutyrate, to increase fat-free mass in cachectic cancer patients.

    CAS  PubMed  Google Scholar 

  85. Ostaszewski, P. et al. The leucine metabolite 3-hydroxy-3-methylbutyrate (HMB) modifies protein turnover in muscles of the laboratory rats and domestic chickens in vitro. J. Anim. Physiol. Anim. Nutr. 84, 1–8 (2000).

    CAS  Google Scholar 

  86. Barber, M. D., Fearon, K. C. H., Tisdale, M. J., McMillan, D. C. & Ross, J. A. Effect of a fish oil-enriched nutritional supplement on metabolic mediators in patients with pancreatic cancer cachexia. Nutr. Cancer 40, 118–124 (2001).

    CAS  PubMed  Google Scholar 

  87. Hussey, H. J. & Tisdale, M. J. Effect of a cachectic factor on carbohydrate metabolism and attenuation by eicosapentaenoic acid. Br. J. Cancer 80, 1231–1235 (1999).

    CAS  PubMed  PubMed Central  Google Scholar 

  88. Smith, H. J., Lorite, M. J. & Tisdale, M. J. Effect of a cancer cachectic factor on protein synthesis/degradation in murine C2C12 myoblasts: modulation by eicosapentaenoic acid. Cancer Res. 59, 5507–5513 (1999).

    CAS  PubMed  Google Scholar 

  89. Tan, C. & Waldmann, T. A. Proteasome inhibitor PS-341, a potential therapeutic agent for adult T-cell leukaemia. Cancer Res. 62, 1083–1086 (2002).

    CAS  PubMed  Google Scholar 

  90. Spataro, V., Norbury, C & Harris, A. L. The ubiquitin-proteasome pathway in cancer. Br. J. Cancer 77, 448–455 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  91. Thompson, M. P., Cooper, S. T., Parry, B. R. & Tuckey, J. A. Increased expression of the mRNA for the hormone-sensitive lipase in adipose tissue of cancer patients. Biochim. Biophys. Acta 1180, 236–242 (1993).

    CAS  PubMed  Google Scholar 

  92. Pisa, P., Stenke, L., Bernell, P., Hanssom, M. & Hast, R. Tumor necrosis factor-α and interferon-α in serum of multiple myeloma patients. Anticancer Res. 10, 817–820 (1990).

    CAS  PubMed  Google Scholar 

  93. Todorov, P. T. et al. Purification and characterization of a tumor lipid-mobilizing factor. Cancer Res. 58, 2353–2358 (1998).

    CAS  PubMed  Google Scholar 

  94. Strang, P. The effect of megestrol acetate on anorexia, weight loss and cachexia in cancer and AIDS patients. Anticancer Res. 17, 657–664 (1997).

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharmaceutical Sciences Research Institute, Aston University, Birmingham, B4 7ET, UK

    Michael J. Tisdale

Authors
  1. Michael J. Tisdale
    View author publications

    You can also search for this author inPubMed Google Scholar

Related links

Related links

DATABASES

Cancer.gov

colorectal cancer

gastric cancer

lung cancer

pancreatic cancer

LocusLink

cathepsin B

CNTF

CRP

E2

E3

fibrinogen

IFN-γ

IL-1

IL-6

IL-8

insulin

leptin

LMF

LPL

MC3R

MC4R

NF-κB

NPY

phospholipase-A2

POMC

PPARγ

STAT3

TNF-α

transferrin

tripeptidyl peptidase II

UCP1

UCP2

UCP3

OMIM

type IIa hyperlipidaemia

FURTHER INFORMATION

Biomedica cachexia information page

Cancernetwork.com anorexia and cachexia page

Family Practice Notebook Cachexia in Cancer

Glossary

CARCASS LIPID

The total fat content of the body when the water has been removed.

BROWN ADIPOSE TISSUE

(BAT). A special type of adipose tissue, the sole function of which is to burn off excess fat and generate heat. It is found in the interscapular region and is most important in the neonate. No BAT has been detected in adult humans, although brown adipocytes might be present in white adipose tissue.

LIPOLYSIS

The process by which triglycerides, which are stored in adipose tissue, are broken down into glycerol and non-esterified fatty acids.

ASTHENIA

Muscle weakness.

KARNOVSKY INDEX

A physician-scored performance scale ranging from 0 to 100 that determines the level of patient activity. A score of 0 means that the patient is totally inactive, a score of 50 means that the patient is just able to get out of bed, and a score of 100 means that the patient is able to function normally.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Tisdale, M. Cachexia in cancer patients. Nat Rev Cancer 2, 862–871 (2002). https://doi.org/10.1038/nrc927

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrc927

Search

Advanced search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing