{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,7]],"date-time":"2026-02-07T09:43:25Z","timestamp":1770457405477,"version":"3.49.0"},"reference-count":96,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2020,10,12]],"date-time":"2020-10-12T00:00:00Z","timestamp":1602460800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Nutrients"],"abstract":"<jats:p>In cancer patients, loss of muscle mass is significantly associated with low tolerability of chemotherapy and poor survival. Despite the great strides in the treatment of cancer, targeted therapies such as tyrosine kinase inhibitors (TKIs) could exacerbate muscle wasting. Over recent years, the impact of skeletal muscle loss during TKI therapy on clinical outcomes has been in the spotlight. In this review, we focus on the different molecular pathways of TKIs potentially involved in muscle wasting. Then, we report the results of the studies assessing the effects of different TKI therapies\u2014such as sorafenib, regorafenib, sunitinib, and lenvatinib\u2014on muscle mass, and highlight their potential clinical implications. Finally, we discuss an integrative nutritional approach to be adopted during TKI treatment. The assessment of muscle mass from computerized tomography imaging could be helpful in predicting toxicity and prognosis in patients treated with TKI such as sorafenib. Early recognition of low muscle mass and effective personalized nutritional support could prevent or attenuate muscle mass wasting. However, the role of nutrition is still overlooked, and future clinical trials are needed to find the optimal nutritional support to countermeasure muscle mass depletion during TKI therapy.<\/jats:p>","DOI":"10.3390\/nu12103101","type":"journal-article","created":{"date-parts":[[2020,10,13]],"date-time":"2020-10-13T21:48:38Z","timestamp":1602625718000},"page":"3101","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":21,"title":["Skeletal Muscle Loss during Multikinase Inhibitors Therapy: Molecular Pathways, Clinical Implications, and Nutritional Challenges"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9165-2367","authenticated-orcid":false,"given":"Emanuele","family":"Rinninella","sequence":"first","affiliation":[{"name":"UOC di Nutrizione Clinica, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9610-0748","authenticated-orcid":false,"given":"Marco","family":"Cintoni","sequence":"additional","affiliation":[{"name":"Scuola di Specializzazione in Scienza dell\u2019Alimentazione, Universit\u00e0 di Roma Tor Vergata, Via Montpellier 1, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6569-1082","authenticated-orcid":false,"given":"Pauline","family":"Raoul","sequence":"additional","affiliation":[{"name":"UOSD di Nutrizione Avanzata in Oncologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4004-9098","authenticated-orcid":false,"given":"Carmelo","family":"Pozzo","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonia","family":"Strippoli","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5924-6238","authenticated-orcid":false,"given":"Francesca Romana","family":"Ponziani","sequence":"additional","affiliation":[{"name":"UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maurizio","family":"Pompili","sequence":"additional","affiliation":[{"name":"UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Dipartimento di Medicina e Chirurgia traslazionale, Universit\u00e0 Cattolica Del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2333-704X","authenticated-orcid":false,"given":"Emilio","family":"Bria","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Dipartimento di Medicina e Chirurgia traslazionale, Universit\u00e0 Cattolica Del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giampaolo","family":"Tortora","sequence":"additional","affiliation":[{"name":"Comprehensive Cancer Center, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Dipartimento di Medicina e Chirurgia traslazionale, Universit\u00e0 Cattolica Del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Gasbarrini","sequence":"additional","affiliation":[{"name":"UOC di Medicina Interna e Gastroenterologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Dipartimento di Medicina e Chirurgia traslazionale, Universit\u00e0 Cattolica Del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8463-7062","authenticated-orcid":false,"given":"Maria Cristina","family":"Mele","sequence":"additional","affiliation":[{"name":"UOSD di Nutrizione Avanzata in Oncologia, Dipartimento di Scienze Mediche e Chirurgiche, Fondazione Policlinico Universitario A. Gemelli IRCCS, Largo A. Gemelli 8, 00168 Rome, Italy"},{"name":"Dipartimento di Medicina e Chirurgia traslazionale, Universit\u00e0 Cattolica Del Sacro Cuore, Largo F. Vito 1, 00168 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,10,12]]},"reference":[{"key":"ref_1","first-page":"3034","article-title":"Approval summary: Imatinib mesylate in the treatment of metastatic and\/or unresectable malignant gastrointestinal stromal tumors","volume":"8","author":"Dagher","year":"2002","journal-title":"Clin. Cancer Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"378","DOI":"10.1056\/NEJMoa0708857","article-title":"Sorafenib in advanced hepatocellular carcinoma","volume":"359","author":"Llovet","year":"2008","journal-title":"N. Engl. J. Med."},{"key":"ref_3","first-page":"97","article-title":"Sunitinib for advanced renal cell cancer","volume":"2","author":"Coppin","year":"2008","journal-title":"Biology"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Mir, O., Coriat, R., Blanchet, B., Durand, J.P., Boudou-Rouquette, P., Michels, J., Ropert, S., Vidal, M., Pol, S., and Chaussade, S. (2012). Sarcopenia predicts early dose-limiting toxicities and pharmacokinetics of sorafenib in patients with hepatocellular carcinoma. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0037563"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2045","DOI":"10.1016\/j.clnu.2019.10.021","article-title":"Muscle mass, assessed at diagnosis by L3-CT scan as a prognostic marker of clinical outcomes in patients with gastric cancer: A systematic review and meta-analysis","volume":"39","author":"Rinninella","year":"2020","journal-title":"Clin. Nutr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"654","DOI":"10.1136\/ijgc-2020-001215","article-title":"Skeletal muscle mass as a prognostic indicator of outcomes in ovarian cancer: A systematic review and meta-analysis","volume":"30","author":"Rinninella","year":"2020","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ejca.2015.12.030","article-title":"Prognostic value of sarcopenia in adults with solid tumours: A meta-analysis and systematic review","volume":"57","author":"Shachar","year":"2016","journal-title":"Eur. J. Cancer"},{"key":"ref_8","first-page":"267","article-title":"Pi3 kinase regulation of skeletal muscle hypertrophy and atrophy","volume":"346","author":"Glass","year":"2010","journal-title":"Curr. Top. Microbiol. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/2044-5040-1-4","article-title":"Regulation of skeletal muscle growth by the IGF1- Akt\/PKB pathway: Insights from genetic models","volume":"1","author":"Schiaffino","year":"2011","journal-title":"Skelet. Muscle."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1139\/h2012-009","article-title":"mTORC1 and the regulation of skeletal muscle anabolism and mass","volume":"37","author":"Adegoke","year":"2012","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1124\/jpet.105.084145","article-title":"Role of tyrosine kinase inhibitors in cancer therapy","volume":"315","author":"Arora","year":"2005","journal-title":"J. Pharm. Exp."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"S3","DOI":"10.1016\/S0959-8049(02)80597-4","article-title":"Regulation and targets of receptor tyrosine kinases","volume":"38","author":"Pawson","year":"2002","journal-title":"Eur. J. Cancer"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1097","DOI":"10.1177\/1947601911423031","article-title":"Vascular endothelial growth factor (VEGFR) and its receptor (VEGFR) signaling in angiogenesis: A crucial target for anti- and pro-angiogenic therapies","volume":"2","author":"Shibuya","year":"2011","journal-title":"Genes Cancer"},{"key":"ref_14","first-page":"29","article-title":"Development of SU5416, a selective small molecule inhibitor of VEGF receptor tyrosine kinase activity, as an anti-angiogenesis agent","volume":"15","author":"Mendel","year":"2000","journal-title":"Anticancer Drug Des."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s10456-009-9160-6","article-title":"Anti-angiogenic tyrosine kinase inhibitors: What is their mechanism of action?","volume":"13","author":"Gotink","year":"2010","journal-title":"Angiogenesis"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"43378","DOI":"10.1038\/srep43378","article-title":"High expression of PDGFR-\u03b2 in prostate cancer stroma is independently associated with clinical and biochemical prostate cancer recurrence","volume":"7","author":"Nordby","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1566","DOI":"10.1007\/s00018-008-7440-8","article-title":"The epidermal growth factor receptor family: Biology driving targeted therapeutics","volume":"65","author":"Wieduwilt","year":"2008","journal-title":"Cell Mol. Life Sci."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1002\/1878-0261.12155","article-title":"Emerging functions of the EGFR in cancer","volume":"12","author":"Sigismund","year":"2018","journal-title":"Mol. Oncol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1186\/s12943-018-0782-4","article-title":"Mechanisms of receptor tyrosine kinase activation in cancer","volume":"17","author":"Du","year":"2018","journal-title":"Mol. Cancer"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1186\/s13578-020-00416-0","article-title":"Roles of the PI3K\/AKT\/mTOR signalling pathways in neurodegenerative diseases and tumours","volume":"10","author":"Xu","year":"2020","journal-title":"Cell Biosci."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1014","DOI":"10.1038\/ncb1101-1014","article-title":"Akt\/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo","volume":"3","author":"Bodine","year":"2001","journal-title":"Nat. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"2276","DOI":"10.1091\/mbc.01-12-0584","article-title":"Akt maintains cell size and survival by increasing mTOR-dependent nutrient uptake","volume":"13","author":"Edinger","year":"2002","journal-title":"Mol. Biol. Cell."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1016\/S0076-6879(05)07047-3","article-title":"Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF\/MEK\/ERK pathway in tumor cells and tyrosine kinases VEGFR\/PDGFR in tumor vasculature","volume":"407","author":"Adnane","year":"2006","journal-title":"Methods Enzym."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1002\/ijc.25864","article-title":"Regorafenib (BAY 73-4506): A new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity","volume":"129","author":"Wilhelm","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"641","DOI":"10.3892\/mco.2016.1015","article-title":"Muscle wasting associated with the long-term use of mTOR inhibitors","volume":"5","author":"Gyawali","year":"2016","journal-title":"Mol. Clin. Oncol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"114","DOI":"10.1016\/j.urology.2017.05.056","article-title":"The Effects of Neoadjuvant Axitinib on Anthropometric Parameters in Patients with Locally Advanced Non-metastatic Renal Cell Carcinoma","volume":"108","author":"Borregales","year":"2017","journal-title":"Urology"},{"key":"ref_27","first-page":"10132","article-title":"Minimal impact of lenvatinib (Lenvima\u00ae) on muscle mass in advanced hepatocellular carcinoma and implications for treatment duration. Two cases from the REFLECT study","volume":"23","author":"Rinninella","year":"2019","journal-title":"Eur. Rev. Med. Pharm. Sci."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1002\/cam4.1909","article-title":"Real-life Practice Experts for HCC (RELPEC) Study Group, HCC 48 Group (hepatocellular carcinoma experts from 48 clinics in Japan). Clinical features of lenvatinib for unresectable hepatocellular carcinoma in real-world conditions: Multicenter analysis","volume":"8","author":"Hiraoka","year":"2019","journal-title":"Cancer Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.clcc.2019.04.003","article-title":"Regorafenib Is Associated With Increased Skeletal Muscle Loss Compared to TAS-102 in Metastatic Colorectal Cancer","volume":"18","author":"Huemer","year":"2019","journal-title":"Clin. Colorectal Cancer"},{"key":"ref_30","first-page":"2198","article-title":"Comparison of skeletal muscle mass loss in patients with metastatic colorectal cancer treated with regorafenib or TAS-102","volume":"24","author":"Hacioglu","year":"2019","journal-title":"J. BUON"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1594","DOI":"10.1093\/annonc\/mdp605","article-title":"Low body mass index and sarcopenia associated with dose-limiting toxicity of sorafenib in patients with renal cell carcinoma","volume":"21","author":"Antoun","year":"2010","journal-title":"Ann. Oncol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1820","DOI":"10.1089\/thy.2018.0784","article-title":"Body Composition in Patients with Radioactive Iodine-Refractory, Advanced Differentiated Thyroid Cancer Treated with Sorafenib or Placebo: A Retrospective Analysis of the Phase III DECISION Trial","volume":"29","author":"Huillard","year":"2019","journal-title":"Thyroid"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1159\/000503829","article-title":"Skeletal muscle loss during tyrosine kinase inhibitor treatment for advanced hepatocellular carcinoma patients","volume":"9","author":"Uchikawa","year":"2020","journal-title":"Liver Cancer"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7587","DOI":"10.1038\/s41598-017-07955-6","article-title":"Early skeletal muscle loss during target therapy is a prognostic biomarker in metastatic renal cell carcinoma patients","volume":"7","author":"Gu","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"735","DOI":"10.1007\/s00280-019-03779-5","article-title":"Changes in skeletal muscle area and lean body mass during pazopanib vs sunitinib therapy for metastatic renal cancer","volume":"83","author":"Demircan","year":"2019","journal-title":"Cancer Chemother. Pharm."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"2401","DOI":"10.1210\/jc.2013-1115","article-title":"Body composition variation and impact of low skeletal muscle mass in patients with advanced medullary thyroid carcinoma treated with vandetanib: Results from a placebo-controlled study","volume":"98","author":"Massicotte","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_37","unstructured":"(2020, January 21). Allegato I Riassunto Delle Caratteristiche del Prodotto. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/nexavar-epar-product-information_it.pdf."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1038\/nrd2130","article-title":"Discovery and development of sorafenib: A multikinase inhibitor for treating cancer","volume":"5","author":"Wilhelm","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"3045","DOI":"10.3892\/ol.2016.5110","article-title":"The Ras\/Raf\/MEK\/ERK signaling pathway and its role in the occurrence and development of HCC","volume":"12","author":"Li","year":"2016","journal-title":"Oncol. Lett."},{"key":"ref_40","first-page":"671","article-title":"Sorafenib inhibits TPA-induced MMP-9 and VEGF expression via suppression of ERK\/NF-\u03baB pathway in hepatocellular carcinoma cells","volume":"26","author":"Chiang","year":"2012","journal-title":"Vivo"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7590","DOI":"10.4081\/ejtm.2018.7590","article-title":"Chemotherapy-induced muscle wasting: Association with NF-\u03baB and cancer cachexia","volume":"28","author":"Damrauer","year":"2018","journal-title":"Eur. J. Transl. Myol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1007\/978-3-319-91442-8_13","article-title":"Lenvatinib: A Tyrosine Kinase Inhibitor of VEGFR 1-3, FGFR 1-4, PDGFR\u03b1, KIT and RE","volume":"211","year":"2018","journal-title":"Recent Results Cancer Res."},{"key":"ref_43","unstructured":"(2020, January 21). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/lenvima-epar-productinformation_it.pdf."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1001\/jama.295.21.2516","article-title":"Sunitinib in patients with metastatic renal cell carcinoma","volume":"295","author":"Motzer","year":"2006","journal-title":"JAMA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/S0140-6736(16)32453-9","article-title":"Regorafenib for patients with hepatocellular carcinoma who progressed on sorafenib treatment (RESORCE): A randomised, double-blind, placebo-controlled, Phase 3 trial","volume":"389","author":"Bruix","year":"2017","journal-title":"Lancet"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Huot, J.R., Essex, A.L., Gutierrez, M., Barreto, R., Wang, M., Waning, D.L., Plotkin, L.I., and Bonetto, A. (2019). Chronic Treatment with Multi-Kinase Inhibitors Causes Differential Toxicities on Skeletal and Cardiac Muscles. Cancers, 11.","DOI":"10.3390\/cancers11040571"},{"key":"ref_47","unstructured":"(2020, October 06). Allegato I Riassunto Delle Caratteristiche del Prodotto. Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/votrient-epar-product-information_it.pdf."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.critrevonc.2010.02.012","article-title":"Pazopanib: Clinicaldevelopment of a potent anti-angiogenic drug","volume":"77","author":"Schutz","year":"2011","journal-title":"Crit Rev. Oncol. Hematol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"395","DOI":"10.1097\/MOU.0000000000000207","article-title":"First-line treatment of metastatic renal cell carcinoma after COMPARZ and PISCES","volume":"25","author":"Schmidinger","year":"2015","journal-title":"Curr. Opin. Urol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"5474","DOI":"10.1200\/JCO.2005.04.192","article-title":"Phase I trial of the oral antiangiogenesis agent AG-013736 in patients with advanced solid tumors: Pharmacokinetic and clinical results","volume":"23","author":"Rugo","year":"2005","journal-title":"J. Clin. Oncol."},{"key":"ref_51","unstructured":"(2020, January 21). Available online: https:\/\/www.ema.europa.eu\/en\/documents\/product-information\/inlyta-epar-productinformation_it.pdf."},{"key":"ref_52","unstructured":"(2020, January 21). Available online: https:\/\/www.accessdata.fda.gov\/drugsatfda_docs\/label\/2012\/022465s-010S-012lbl.pdf."},{"key":"ref_53","doi-asserted-by":"crossref","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":"Borges","year":"2016","journal-title":"Springerplus"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1034","DOI":"10.1038\/bjc.2013.58","article-title":"Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients","volume":"108","author":"Huillard","year":"2013","journal-title":"Br. J. Cancer."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1097\/COC.0000000000000061","article-title":"Body Composition by Computed Tomography as a Predictor of Toxicity in Patients With Renal Cell Carcinoma Treated With Sunitinib","volume":"40","author":"Cushen","year":"2017","journal-title":"Am. J. Clin. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"339.e17","DOI":"10.1016\/j.urolonc.2015.01.011","article-title":"Sarcopenia as a predictor of overall survival after cytoreductive nephrectomy for metastatic renal cell carcinoma","volume":"33","author":"Sharma","year":"2015","journal-title":"Urol. Oncol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.juro.2015.08.071","article-title":"Prognostic Significance of Sarcopenia in Patients with Metastatic Renal Cell Carcinoma","volume":"195","author":"Fukushima","year":"2016","journal-title":"J. Urol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1177\/2050640618781188","article-title":"Sarcopenia is associated with reduced survival in patients with advanced hepatocellular carcinoma undergoing sorafenib treatment","volume":"6","author":"Antonelli","year":"2018","journal-title":"United Eur. Gastroenterol. J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"193","DOI":"10.1159\/000504604","article-title":"Morimoto, M.; et al. Skeletal muscle mass influences tolerability and prognosis in hepatocellular carcinoma patients treated with lenvatinib","volume":"9","author":"Uojima","year":"2019","journal-title":"Liver Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"107","DOI":"10.5604\/16652681.1226821","article-title":"Sarcopenia predicts reduced survival in patients with hepatocellular carcinoma at first diagnosis","volume":"16","author":"Begini","year":"2017","journal-title":"Ann. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1007\/s13668-017-0216-8","article-title":"The Challenges of Nutritional Assessment in Cirrhosis","volume":"6","author":"Molfino","year":"2017","journal-title":"Curr. Nutr. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"268","DOI":"10.1016\/j.jpge.2015.06.004","article-title":"Nutrition in Chronic Liver Disease","volume":"22","author":"Silva","year":"2015","journal-title":"GE Port. J. Gastroenterol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/j.clnu.2012.05.009","article-title":"Nutritional status, cachexia and survival in patients with advanced colorectal carcinoma. Different assessment criteria for nutritional status provide unequal results","volume":"32","author":"Thoresen","year":"2013","journal-title":"Clin. Nutr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1339","DOI":"10.1200\/JCO.2015.63.6043","article-title":"Loss of Muscle Mass During Chemotherapy Is Predictive for Poor Survival of Patients With Metastatic Colorectal Cancer","volume":"34","author":"Versteeg","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"803","DOI":"10.1002\/jcsm.12436","article-title":"Skeletal muscle mass loss and dose-limiting toxicities in metastatic colorectal cancer patients","volume":"10","author":"Kurk","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1518","DOI":"10.1007\/s12094-019-02080-4","article-title":"Relation between sarcopenia and dose-limiting toxicity in patients with metastatic colorectal cancer who received regorafenib","volume":"21","author":"Sunal","year":"2019","journal-title":"Clin. Transl. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"489","DOI":"10.1093\/ajcn\/65.2.489","article-title":"Splanchnic and whole-body leucine kinetics in young and elderly men","volume":"65","author":"Boirie","year":"1997","journal-title":"Am. J. Clin. Nutr."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1093\/ageing\/afy169","article-title":"Sarcopenia: Revised European consensus on definition and diagnosis","volume":"48","author":"Bahat","year":"2019","journal-title":"Age Ageing"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1187","DOI":"10.1016\/j.clnu.2017.06.017","article-title":"ESPEN expert group recommendations for action against cancer-related malnutrition","volume":"36","author":"Arends","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1002\/jcsm.12483","article-title":"Sarcopenia: A Time for Action. An SCWD Position Paper","volume":"10","author":"Bauer","year":"2019","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1007\/s11739-018-1944-5","article-title":"May nutritional status worsen during hospital stay? A sub-group analysis from a cross-sectional study","volume":"14","author":"Rinninella","year":"2019","journal-title":"Intern. Emerg. Med."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/j.clnu.2016.07.015","article-title":"ESPEN guidelines on nutrition in cancer patients","volume":"36","author":"Arends","year":"2017","journal-title":"Clin. Nutr."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"997","DOI":"10.1139\/H08-075","article-title":"A practical and precise approach to quantification of body composition in cancer patients using computed tomography images acquired during routine care","volume":"33","author":"Mourtzakis","year":"2008","journal-title":"Appl. Physiol. Nutr. Metab."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"527","DOI":"10.1002\/jcsm.12221","article-title":"Psoas as a sentinel muscle for sarcopenia: A flawed premise","volume":"8","author":"Baracos","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"630","DOI":"10.1002\/jcsm.12180","article-title":"Psoas muscle area is not representative of total skeletal muscle area in the assessment of sarcopenia in ovarian cancer","volume":"8","author":"Rutten","year":"2017","journal-title":"J. Cachexia Sarcopenia Muscle"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"2312","DOI":"10.1016\/S0140-6736(18)32776-4","article-title":"Individualised nutritional support in medical inpatients at nutritional risk: A randomised clinical trial","volume":"393","author":"Schuetz","year":"2019","journal-title":"Lancet"},{"key":"ref_77","unstructured":"Kaegi-Braun, N., Tribolet, P., Gomes, F., Fehr, R., Baechli, V., Geiser, M., Deiss, M., Kutz, A., Bregenzer, T., and Hoess, C. (2020). Six-month outcomes after individualized nutritional support during the hospital stay in medical patients at nutritional risk: Secondary analysis of a prospective randomized trial. Clin. Nutr., S0261-5614(20)30435-0."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.nut.2018.01.013","article-title":"NutriCatt protocol in the Enhanced Recovery After Surgery (ERAS) program for colorectal surgery: The nutritional support improves clinical and cost-effectiveness outcomes","volume":"50","author":"Rinninella","year":"2018","journal-title":"Nutrition"},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Ardito, F., Lai, Q., Rinninella, E., Mimmo, A., Vellone, M., Panettieri, E., Adducci, E., Cintoni, M., Mele, M.C., and Gasbarrini, A. (2020). The impact of personalized nutritional support on postoperative outcome within the enhanced recovery after surgery (ERAS) program for liver resections: Results from the NutriCatt protocol. Updates Surg.","DOI":"10.1007\/s13304-020-00787-6"},{"key":"ref_80","first-page":"472","article-title":"Evolution of nutritional status and survival in patients with cancer on tyrosine kinase inhibitors treatment","volume":"66","author":"Ribed","year":"2019","journal-title":"Endocrinol. Diabetes Nutr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"ii10","DOI":"10.1093\/annonc\/mdx809","article-title":"Muscle protein anabolism in advanced cancer patients: Response to protein and amino acids support, and to physical activity","volume":"29","author":"Antoun","year":"2018","journal-title":"Ann. Oncol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1055\/s-2007-1019316","article-title":"In vivo effects of branched chain amino acids on muscle protein synthesis in fasted rats","volume":"13","author":"Buse","year":"1981","journal-title":"Horm. Metab. Res."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1042\/bj2540579","article-title":"Amino acid infusion increases the sensitivity of muscle protein synthesis in vivo to insulin. Effect of branched chain amino acids","volume":"254","author":"Garlick","year":"1988","journal-title":"Biochem. J."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/s12970-017-0184-9","article-title":"Branched-chain amino acids and muscle protein synthesis in humans: Myth or reality?","volume":"14","author":"Wolfe","year":"2017","journal-title":"J. Int. Soc. Sports Nutr."},{"key":"ref_85","first-page":"E928","article-title":"Leucine as a regulator of whole body and skeletal muscle protein metabolism in humans","volume":"263","author":"Nair","year":"1992","journal-title":"Am. J. Physiol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1002\/1097-0142(19860701)58:1<147::AID-CNCR2820580126>3.0.CO;2-I","article-title":"Improved protein kinetics and albumin synthesis by branched chain amino acid-enriched total parenteral nutrition in cancer cachexia. A prospective randomized crossover trial","volume":"58","author":"Tayek","year":"1986","journal-title":"Cancer"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"149","DOI":"10.1002\/bjs.1800760215","article-title":"Branched chain amino acids as the protein component of parenteral nutrition in cancer cachexia","volume":"76","author":"Hunter","year":"1989","journal-title":"Br. J. Surg."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1111\/hepr.12125","article-title":"Effect of treatment with branched-chain amino acids during sorafenib therapy for unresectable hepatocellular carcinoma","volume":"44","author":"Takeda","year":"2014","journal-title":"Hepatol. Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/j.1872-034X.2008.00435.x","article-title":"Role of branched-chain amino acids in management of cirrhosis and hepatocellular carcinoma","volume":"38","author":"Lam","year":"2008","journal-title":"Hepatol. Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.nutres.2008.12.005","article-title":"A snack enriched with oral branched-chain amino acids prevents a fall in albumin in patients with liver cirrhosis undergoing chemoembolization for hepatocellular carcinoma","volume":"29","author":"Takeshita","year":"2009","journal-title":"Nutr. Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1111\/j.1872-034X.2012.00969.x","article-title":"Late-evening snack with branched-chain amino acids improves liver function after radiofrequency ablation for hepatocellular carcinoma","volume":"42","author":"Morihara","year":"2012","journal-title":"Hepatol. Res."},{"key":"ref_92","first-page":"1491","article-title":"Oral branched-chain amino acids administration improves impaired liver dysfunction after radiofrequency ablation therapy for hepatocellular carcinoma","volume":"56","author":"Ishikawa","year":"2009","journal-title":"Hepatogastroenterology"},{"key":"ref_93","unstructured":"Kimball, S.R., and Jefferson, L.S. (2004). Amino acids as regulators of gene expression. Nutr. Metab., 17."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"1547S","DOI":"10.1093\/jn\/135.6.1547S","article-title":"Hormonal and signaling role of branched-chain amino acids","volume":"135","author":"Nair","year":"2005","journal-title":"J. Nutr."},{"key":"ref_95","first-page":"235","article-title":"Chemotherapy for hepatocellular carcinoma: Current evidence and future perspectives","volume":"5","author":"Rinninella","year":"2017","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/S0002-9610(02)00823-1","article-title":"Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine","volume":"183","author":"May","year":"2002","journal-title":"Am. J. Surg."}],"container-title":["Nutrients"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/10\/3101\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:19:29Z","timestamp":1760177969000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2072-6643\/12\/10\/3101"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,10,12]]},"references-count":96,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2020,10]]}},"alternative-id":["nu12103101"],"URL":"https:\/\/doi.org\/10.3390\/nu12103101","relation":{},"ISSN":["2072-6643"],"issn-type":[{"value":"2072-6643","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,10,12]]}}}