{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T14:42:15Z","timestamp":1780584135436,"version":"3.54.1"},"reference-count":55,"publisher":"Frontiers Media SA","funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA122596"],"award-info":[{"award-number":["R01CA122596"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["R01CA194593"],"award-info":[{"award-number":["R01CA194593"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institute of General Medical Sciences","doi-asserted-by":"publisher","award":["R01GM092758"],"award-info":[{"award-number":["R01GM092758"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100005979","name":"Lustgarten Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005979","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"National Institute of Diabetes and Digestive and Kidney Diseases","doi-asserted-by":"publisher","award":["R01DK096167"],"award-info":[{"award-number":["R01DK096167"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006976","name":"Lilly Endowment","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100006976","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100006733","name":"Indiana University","doi-asserted-by":"publisher","award":["Simon Cancer Center"],"award-info":[{"award-number":["Simon Cancer Center"]}],"id":[{"id":"10.13039\/100006733","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008113","name":"Indiana University-Purdue University Indianapolis","doi-asserted-by":"publisher","award":["Center for Pancreatic Cancer Research"],"award-info":[{"award-number":["Center for Pancreatic Cancer Research"]}],"id":[{"id":"10.13039\/100008113","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"DOI":"10.3389\/fphys.2016.00682","type":"journal-article","created":{"date-parts":[[2017,1,18]],"date-time":"2017-01-18T03:48:33Z","timestamp":1484711313000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["The MEK-Inhibitor Selumetinib Attenuates Tumor Growth and Reduces IL-6 Expression but Does Not Protect against Muscle Wasting in Lewis Lung Cancer Cachexia"],"prefix":"10.3389","volume":"7","author":[{"given":"Ernie D.","family":"Au","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditya P.","family":"Desai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Leonidas G.","family":"Koniaris","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Teresa A.","family":"Zimmers","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2017,1,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1356","DOI":"10.1158\/1078-0432.CCR-06-2307","article-title":"Cancer cachexia signaling pathways continue to emerge yet much still points to the proteasome","volume":"13","author":"Acharyya","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1210\/endo.143.2.8648","article-title":"Early stimulation and late inhibition of extracellular signal-regulated kinase 1\/2 phosphorylation by IGF-I: a potential mechanism mediating the switch in IGF-I action on skeletal muscle cell differentiation","volume":"143","author":"Adi","year":"2002","journal-title":"Endocrinology"},{"key":"B3","doi-asserted-by":"publisher","first-page":"100","DOI":"10.1016\/j.coph.2015.04.003","article-title":"Cachexia and sarcopenia: mechanisms and potential targets for intervention","volume":"22","author":"Argil\u00e9s","year":"2015","journal-title":"Curr. Opin. Pharmacol."},{"key":"B4","doi-asserted-by":"publisher","first-page":"43442","DOI":"10.18632\/oncotarget.9779","article-title":"Chemotherapy-related cachexia is associated with mitochondrial depletion and the activation of ERK1\/2 and p38 MAPKs","volume":"7","author":"Barreto","year":"2016","journal-title":"Oncotarget"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1663","DOI":"10.1517\/14712598.2011.627850","article-title":"A humanized anti-IL-6 antibody (ALD518) in non-small cell lung cancer","volume":"11","author":"Bayliss","year":"2011","journal-title":"Expert Opin. Biol. Ther."},{"key":"B6","doi-asserted-by":"publisher","first-page":"2357","DOI":"10.1200\/JCO.2010.33.9473","article-title":"Multi-institutional phase II study of selumetinib in patients with metastatic biliary cancers","volume":"29","author":"Bekaii-Saab","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1186\/s40064-016-2197-2","article-title":"Skeletal muscle wasting and renewal: a pivotal role of myokine IL-6","volume":"5","author":"Beliz\u00e1rio","year":"2016","journal-title":"Springerplus"},{"key":"B8","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.1007\/s00520-010-0972-0","article-title":"Animal models of the cancer anorexia-cachexia syndrome","volume":"19","author":"Bennani-Baiti","year":"2011","journal-title":"Support Care Cancer"},{"key":"B9","doi-asserted-by":"publisher","first-page":"1548","DOI":"10.1016\/j.bbrc.2009.12.123","article-title":"Acute inhibition of myostatin-family proteins preserves skeletal muscle in mouse models of cancer cachexia","volume":"391","author":"Benny Klimek","year":"2010","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B10","doi-asserted-by":"publisher","first-page":"E410","DOI":"10.1152\/ajpendo.00039.2012","article-title":"JAK\/STAT3 pathway inhibition blocks skeletal muscle wasting downstream of IL-6 and in experimental cancer cachexia","volume":"303","author":"Bonetto","year":"2012","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"B11","doi-asserted-by":"publisher","first-page":"e22538","DOI":"10.1371\/journal.pone.0022538","article-title":"STAT3 activation in skeletal muscle links muscle wasting and the acute phase response in cancer cachexia","volume":"6","author":"Bonetto","year":"2011","journal-title":"PLoS ONE"},{"key":"B12","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1002\/jcsm.12023","article-title":"Ghrelin prevents tumour- and cisplatin-induced muscle wasting: characterization of multiple mechanisms involved","volume":"6","author":"Chen","year":"2015","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B13","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1002\/jcsm.12104","article-title":"Doxorubicin caused severe hyperglycaemia and insulin resistance, mediated by inhibition in AMPk signalling in skeletal muscle","volume":"7","author":"de Lima Junior","year":"2016","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B14","first-page":"3347","article-title":"Limited impact of total parenteral nutrition on nutritional status during treatment for small cell lung cancer","volume":"45","author":"Evans","year":"1985","journal-title":"Cancer Res."},{"key":"B15","doi-asserted-by":"publisher","first-page":"993","DOI":"10.1586\/17474124.2015.1040763","article-title":"MEK 1\/2 inhibitors in the treatment of hepatocellular carcinoma","volume":"9","author":"Facciorusso","year":"2015","journal-title":"Expert. Rev. Gastroenterol. Hepatol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"153","DOI":"10.1016\/j.cmet.2012.06.011","article-title":"Cancer cachexia: mediators, signaling, and metabolic pathways","volume":"16","author":"Fearon","year":"2012","journal-title":"Cell Metab."},{"key":"B17","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1016\/S1470-2045(10)70218-7","article-title":"Definition and classification of cancer cachexia: an international consensus","volume":"12","author":"Fearon","year":"2011","journal-title":"Lancet Oncol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"581","DOI":"10.1016\/0898-6568(94)90041-8","article-title":"The mitogen activated protein kinase signal transduction pathway: from the cell surface to the nucleus","volume":"6","author":"Guan","year":"1994","journal-title":"Cell. Signal."},{"key":"B19","doi-asserted-by":"publisher","first-page":"26","DOI":"10.1186\/s13395-016-0098-2","article-title":"ActRII blockade protects mice from cancer cachexia and prolongs survival in the presence of anti-cancer treatments","volume":"6","author":"Hatakeyama","year":"2016","journal-title":"Skelet. Muscle"},{"key":"B20","doi-asserted-by":"publisher","first-page":"319","DOI":"10.1016\/S2213-2600(15)00026-0","article-title":"Targeting of MEK in lung cancer therapeutics","volume":"3","author":"Heigener","year":"2015","journal-title":"Lancet Respir. Med."},{"key":"B21","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1172\/JCI81655","article-title":"TRAF6 regulates satellite stem cell self-renewal and function during regenerative myogenesis","volume":"126","author":"Hindi","year":"2016","journal-title":"J. Clin. Invest."},{"key":"B22","doi-asserted-by":"publisher","first-page":"144","DOI":"10.1136\/gut.52.1.144","article-title":"Mitogen activated protein (MAP) kinase signal transduction pathways and novel anti-inflammatory targets","volume":"52","author":"Hommes","year":"2003","journal-title":"Gut"},{"key":"B23","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1016\/j.molonc.2012.09.002","article-title":"MEK inhibitors reverse resistance in epidermal growth factor receptor mutation lung cancer cells with acquired resistance to gefitinib","volume":"7","author":"Huang","year":"2013","journal-title":"Mol. Oncol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"C834","DOI":"10.1152\/ajpcell.00579.2003","article-title":"The molecular basis of skeletal muscle atrophy","volume":"287","author":"Jackman","year":"2004","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1910","DOI":"10.1016\/j.cellsig.2009.08.008","article-title":"MEK1 plays contrary stage-specific roles in skeletal myogenic differentiation","volume":"21","author":"Jo","year":"2009","journal-title":"Cell. Signal."},{"key":"B26","doi-asserted-by":"publisher","first-page":"187","DOI":"10.1016\/j.bbamcr.2004.11.002","article-title":"Leukemia inhibitory factor blocks early differentiation of skeletal muscle cells by activating ERK","volume":"1743","author":"Jo","year":"2005","journal-title":"Biochim. Biophys. Acta"},{"key":"B27","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1002\/1097-4652(200101)186:1104::AID-JCP10153.0.CO;2-0","article-title":"ERK1\/2 is required for myoblast proliferation but is dispensable for muscle gene expression and cell fusion","volume":"186","author":"Jones","year":"2001","journal-title":"J. Cell. Physiol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"1425","DOI":"10.1016\/j.bbrc.2006.05.051","article-title":"ERK2 is required for efficient terminal differentiation of skeletal myoblasts","volume":"345","author":"Li","year":"2006","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"B29","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/j.bone.2015.03.015","article-title":"Inflammation induced loss of skeletal muscle","volume":"80","author":"Londhe","year":"2015","journal-title":"Bone"},{"key":"B30","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1016\/j.cmet.2007.11.001","article-title":"FoxO3 controls autophagy in skeletal muscle in vivo","volume":"6","author":"Mammucari","year":"2007","journal-title":"Cell Metab."},{"key":"B31","doi-asserted-by":"publisher","first-page":"128","DOI":"10.1016\/j.ygyno.2014.01.008","article-title":"MEK1\/2 inhibitors in the treatment of gynecologic malignancies","volume":"133","author":"Miller","year":"2014","journal-title":"Gynecol. Oncol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"907","DOI":"10.1111\/j.1469-8749.2007.00907.x","article-title":"Increased efficacy and decreased systemic-effects of botulinum toxin A injection after active or passive muscle manipulation","volume":"49","author":"Minamoto","year":"2007","journal-title":"Dev. Med. Child Neurol"},{"key":"B33","doi-asserted-by":"publisher","first-page":"19679","DOI":"10.1074\/jbc.M109.017319","article-title":"Cardiotrophin-1 maintains the undifferentiated state in skeletal myoblasts","volume":"284","author":"Miyake","year":"2009","journal-title":"J. Biol. Chem."},{"key":"B34","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1097\/SPC.0000000000000091","article-title":"Role of interleukin-6 in cachexia: therapeutic implications","volume":"8","author":"Narsale","year":"2014","journal-title":"Curr. Opin. Support Palliat. Care"},{"key":"B35","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.pharmthera.2013.10.001","article-title":"MEK in cancer and cancer therapy","volume":"141","author":"Neuzillet","year":"2014","journal-title":"Pharmacol. Therapeut."},{"key":"B36","doi-asserted-by":"publisher","first-page":"10123","DOI":"10.1038\/ncomms10123","article-title":"TAK1 modulates satellite stem cell homeostasis and skeletal muscle repair","volume":"6","author":"Ogura","year":"2015","journal-title":"Nat. Commun."},{"key":"B37","doi-asserted-by":"crossref","first-page":"1889","DOI":"10.1002\/eji.1830230824","article-title":"Cachexia and the acute-phase protein response in inflammation are regulated by interleukin-6","volume":"23","author":"Oldenburg","year":"1993","journal-title":"Eur. J. Immunol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"e13604","DOI":"10.1371\/journal.pone.0013604","article-title":"Muscle wasting and impaired myogenesis in tumor bearing mice are prevented by ERK inhibition","volume":"5","author":"Penna","year":"2010","journal-title":"PLoS ONE"},{"key":"B39","doi-asserted-by":"publisher","first-page":"1583","DOI":"10.1038\/bjc.2012.144","article-title":"Skeletal muscle anabolism is a side effect of therapy with the MEK inhibitor: selumetinib in patients with cholangiocarcinoma","volume":"106","author":"Prado","year":"2012","journal-title":"Br. J. Cancer"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-16-0324","article-title":"Selumetinib attenuate skeletal muscle wasting in murine cachexia model through ERK inhibition and AKT activation","author":"Quan-Jun","year":"2016","journal-title":"Mol. Cancer Ther."},{"key":"B41","doi-asserted-by":"publisher","first-page":"1738","DOI":"10.1126\/science.286.5445.1738","article-title":"Differentiation stage-specific inhibition of the Raf-MEK-ERK pathway by Akt","volume":"286","author":"Rommel","year":"1999","journal-title":"Science"},{"key":"B42","doi-asserted-by":"publisher","first-page":"6619","DOI":"10.1158\/1078-0432.CCR-08-2958","article-title":"The mitogen-activated protein\/extracellular signal-regulated kinase kinase 1\/2 inhibitor AZD6244 (ARRY-142886) enhances the radiation responsiveness of lung and colorectal tumor xenografts","volume":"15","author":"Shannon","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"B43","doi-asserted-by":"publisher","first-page":"281","DOI":"10.1007\/978-3-319-22539-5_12","article-title":"Treatment of Uveal Melanoma","volume":"167","author":"Shoushtari","year":"2016","journal-title":"Cancer Treat Res."},{"key":"B44","doi-asserted-by":"publisher","first-page":"11177","DOI":"10.1074\/jbc.M115.641514","article-title":"Inhibition of Stat3 activation suppresses caspase-3 and the ubiquitin-proteasome system, leading to preservation of muscle mass in cancer cachexia","volume":"290","author":"Silva","year":"2015","journal-title":"J. Biol. Chem."},{"key":"B45","doi-asserted-by":"publisher","first-page":"1681","DOI":"10.1172\/JCI115767","article-title":"Evidence for the involvement of interleukin 6 in experimental cancer cachexia","volume":"89","author":"Strassmann","year":"1992","journal-title":"J. Clin. Invest."},{"key":"B46","doi-asserted-by":"publisher","first-page":"1656","DOI":"10.1182\/blood-2007-03-081240","article-title":"Targeting MEK induces myeloma-cell cytotoxicity and inhibits osteoclastogenesis","volume":"110","author":"Tai","year":"2007","journal-title":"Blood"},{"key":"B47","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1002\/jcsm.12035","article-title":"A multifactorial anti-cachectic approach for cancer cachexia in a rat model undergoing chemotherapy","volume":"7","author":"Toledo","year":"2016","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"B48","doi-asserted-by":"publisher","first-page":"1648","DOI":"10.1038\/bjc.2012.129","article-title":"Intrinsic resistance to selumetinib, a selective inhibitor of MEK1\/2, by cAMP-dependent protein kinase A activation in human lung and colorectal cancer cells","volume":"106","author":"Troiani","year":"2012","journal-title":"Br. J. Cancer"},{"key":"B49","doi-asserted-by":"publisher","first-page":"174","DOI":"10.1016\/j.tem.2012.10.006","article-title":"Cancer cachexia: malignant inflammation, tumorkines, and metabolic mayhem","volume":"24","author":"Tsoli","year":"2013","journal-title":"Trends Endocrinol. Metab."},{"key":"B50","doi-asserted-by":"publisher","first-page":"68","DOI":"10.1016\/j.semcdb.2015.10.039","article-title":"Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia","volume":"54","author":"Tsoli","year":"2016","journal-title":"Semin. Cell Dev. Biol"},{"key":"B51","doi-asserted-by":"publisher","first-page":"e24650","DOI":"10.1371\/journal.pone.0024650","article-title":"The regulation of skeletal muscle protein turnover during the progression of cancer cachexia in the ApcMin\/+ mouse","volume":"6","author":"White","year":"2011","journal-title":"PLoS ONE"},{"key":"B52","doi-asserted-by":"publisher","first-page":"1576","DOI":"10.1158\/1078-0432.CCR-06-1150","article-title":"Biological characterization of ARRY-142886 (AZD6244), a potent, highly selective mitogen-activated protein kinase kinase 1\/2 inhibitor","volume":"13","author":"Yeh","year":"2007","journal-title":"Clin. Cancer Res."},{"key":"B53","doi-asserted-by":"crossref","first-page":"11435","DOI":"10.1016\/S0021-9258(18)82142-1","article-title":"Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2","volume":"268","author":"Zheng","year":"1993","journal-title":"J. Biol. Chem."},{"key":"B54","doi-asserted-by":"publisher","first-page":"531","DOI":"10.1016\/j.cell.2010.07.011","article-title":"Reversal of cancer cachexia and muscle wasting by ActRIIB antagonism leads to prolonged survival","volume":"142","author":"Zhou","year":"2010","journal-title":"Cell"},{"key":"B55","doi-asserted-by":"publisher","first-page":"28","DOI":"10.1016\/j.semcdb.2016.02.009","article-title":"STAT3 in the systemic inflammation of cancer cachexia","volume":"54","author":"Zimmers","year":"2016","journal-title":"Semin. Cell Dev. Biol."}],"container-title":["Frontiers in Physiology"],"original-title":[],"link":[{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphys.2016.00682\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,7,21]],"date-time":"2022-07-21T23:33:01Z","timestamp":1658446381000},"score":1,"resource":{"primary":{"URL":"http:\/\/journal.frontiersin.org\/article\/10.3389\/fphys.2016.00682\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2017,1,18]]},"references-count":55,"URL":"https:\/\/doi.org\/10.3389\/fphys.2016.00682","relation":{},"ISSN":["1664-042X"],"issn-type":[{"value":"1664-042X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2017,1,18]]}}}