Skeletal muscle loss appears to be the most significant clinical event in cancer cachexia and is associated with a poor outcome. With regard to such muscle loss, despite extensive study in a range of models, there is ongoing debate as to whether a reduction in protein synthesis, an increase in degradation or a combination of both is the more relevant. Each model differs in terms of key mediators and the pathways activated in skeletal muscle. Certain models do suggest that decreased synthesis accompanied by enhanced protein degradation via the ubiquitin proteasome pathway (UPP) is important. Murine models tend to involve rapid development of cachexia and may represent more acute muscle atrophy rather than the chronic wasting observed in humans. There is a paucity of human data both at a basic descriptive level and at a molecular/mechanism level. Progress in treating the human form of cancer cachexia can only move forwards through carefully designed large randomised controlled clinical trials of specific therapies with validated biomarkers of relevance to underlying mechanisms. This article is part of a Directed Issue entitled: Molecular basis of muscle wasting.
Keywords: ACTRIIB; APC; APPR; ARC; ATP; C-26; CHO; COPD; CRPc; CSA; Cachexia; Cancer; Chinese hamster ovary; DGC; DM; DNA; Degradation; EDL; EIF3F; F-box protein 40; F-bxo40; FCSA; FOXO; ICU; IFN; IGF; IL; IRS; JAK; Janus associated kinase; LBM; LLC; Lewis lung carcinoma; MA; MAC16; MAFbx; MAPK; MCR; MRI; MSH; MURF-1; Muscle; MyHC; NFκB; NPY; NSCLC; PBMC; PI3K; POMC; QoL; RNA; STAT; Synthesis; T helper; T(h); TA; TAM; TGF; TNF; TWEAK; UPP; Ub; activin receptor type-2B; acute phase protein response; adenomatosis polyposis coli; adenosine-5′-triphosphate; arcuate nucleus; chronic obstructive pulmonary disease; colon-26 adenocarcinoma mouse model; cross sectional area; deoxyribonucleic acid; diabetes mellitus; dystrophin glycoprotein complex; eukaryotic translation initiation factor 3 subunit F; extensor digitorum longus; fibre cross sectional area; forkhead box class O transcription factor; insulin receptor substrate; insulin-like growth factor; intensive care unit; interferon; interleukin; lean body mass; mAb; mRNA; mTOR; magnetic resonance imaging; mammalian target of rapamycin; megestrol acetate; melanocortin receptor; melanocyte-stimulating hormone; messenger ribonucleic acid; mitogen activated kinase; monoclonal antibody; murine adenocarcinoma 16 mouse model; muscle-specific F-box (also known as atrogin-1); muscle-specific RING finger-1; myosin heavy chain; neuropeptide Y; non-small cell lung cancer; nuclear factor-κβ; peripheral blood mononuclear cell; phosphatidylinositol 3-kinase; pro-opiomelanocortin; quality of life; reactive protein; ribonucleic acid; signal transducer and activator of transcription; tibialis anterior; transforming growth factor; tumour necrosis factor; tumour necrosis factor-like weak inducer of apoptosis; tumour-associated macrophage; ubiquitin; ubiquitin-proteasome pathway.
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