{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T11:47:39Z","timestamp":1793533659803,"version":"4.5.0"},"reference-count":99,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T00:00:00Z","timestamp":1626912000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K09336"],"award-info":[{"award-number":["21K09336"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Dedifferentiated liposarcoma (DDL) is defined as the transition from well-differentiated liposarcoma (WDL)\/atypical lipomatous tumor (ALT) to non-lipogenic sarcoma, which arises mostly in the retroperitoneum and deep soft tissue of proximal extremities. It is characterized by a supernumerary ring and giant marker chromosomes, both of which contain amplified sequences of 12q13-15 including murinedouble minute 2 (MDM2) and cyclin-dependent kinase 4 (CDK4) cell cycle oncogenes. Detection of MDM2 (and\/or CDK4) amplification serves to distinguish DDL from other undifferentiated sarcomas. Recently, CTDSP1\/2-DNM3OS fusion genes have been identified in a subset of DDL. However, the genetic events associated with dedifferentiation of WDL\/ALT remain to be clarified. The standard treatment for localized DDL is surgery, with or without radiotherapy. In advanced disease, the standard first-line therapy is an anthracycline-based regimen, with either single-agent anthracycline or anthracycline in combination with the alkylating agent ifosfamide. Unfortunately, this regimen has not necessarily led to a satisfactory clinical outcome. Recent advances in the understanding of the pathogenesis of DDL may allow for the development of more-effective innovative therapeutic strategies. This review provides an overview of the current knowledge on the clinical presentation, pathogenesis, histopathology and treatment of DDL.<\/jats:p>","DOI":"10.3390\/jcm10153230","type":"journal-article","created":{"date-parts":[[2021,7,22]],"date-time":"2021-07-22T22:35:31Z","timestamp":1626993331000},"page":"3230","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":75,"title":["Biology and Management of Dedifferentiated Liposarcoma: State of the Art and Perspectives"],"prefix":"10.3390","volume":"10","author":[{"given":"Jun","family":"Nishio","sequence":"first","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shizuhide","family":"Nakayama","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuki","family":"Nabeshima","sequence":"additional","affiliation":[{"name":"Department of Pathology, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takuaki","family":"Yamamoto","sequence":"additional","affiliation":[{"name":"Department of Orthopaedic Surgery, Faculty of Medicine, Fukuoka University, 7-45-1 Nanakuma, Jonan-ku, Fukuoka 814-0180, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,22]]},"reference":[{"key":"ref_1","unstructured":"The WHO Classification of Tumors Editorial Board (2020). WHO Classification of Tumours of Soft Tissue and Bone, IARC Press. [5th ed.]."},{"key":"ref_2","first-page":"1","article-title":"Contributions of Cytogenetics and Molecular Cytogenetics to the Diagnosis of Adipocytic Tumors","volume":"2011","author":"Nishio","year":"2011","journal-title":"J. Biomed. Biotechnol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41467-019-13286-z","article-title":"Integrated exome and RNA sequencing of dedifferentiated liposarcoma","volume":"10","author":"Hirata","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1111\/his.13957","article-title":"Atypical lipomatous tumour\/well-differentiated liposarcoma and de-differentiated liposarcoma in patients aged \u226440 years: A study of 116 patients","volume":"75","author":"Waters","year":"2019","journal-title":"Histopathology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1053\/j.semdp.2019.02.006","article-title":"Well-differentiated liposarcoma and dedifferentiated liposarcoma: An updated review","volume":"36","author":"Thway","year":"2019","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1097\/00000478-199703000-00002","article-title":"Dedifferentiated liposarcoma: A clinicopathological analysis of 155 cases with a proposal for an expanded definition of dedifferentiation","volume":"21","author":"Henricks","year":"1997","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1097\/PAP.0000000000000101","article-title":"Dedifferentiated liposarcoma: Updates on morphology, genetics and therapeutic strategies","volume":"23","author":"Thway","year":"2016","journal-title":"Adv. Anat. Pathol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2550","DOI":"10.1097\/CORR.0000000000001338","article-title":"What are the results of localized dedifferentiated liposarcomas in the extremities?","volume":"478","author":"Nakata","year":"2020","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1094","DOI":"10.1093\/jjco\/hyr098","article-title":"Primary (de novo) dedifferentiated liposarcoma in the extremities: A multi-institution Tohoku Musculoskeletal Tumor Society study of 18 cases in northern Japan","volume":"41","author":"Okada","year":"2011","journal-title":"Jpn. J. Clin. Oncol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1148\/rg.255055106","article-title":"From the archives of the AFIP: Imaging of musculoskeletal liposarcoma with radiologic-pathologic correlation","volume":"25","author":"Murphey","year":"2005","journal-title":"RadioGraphics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1155\/2020\/8363986","article-title":"PET\/CT Imaging as a Diagnostic Tool in Distinguishing Well-Differentiated versus Dedifferentiated Liposarcoma","volume":"2020","author":"Parkes","year":"2020","journal-title":"Sarcoma"},{"key":"ref_12","first-page":"74","article-title":"18F-FDG PET\/CT imaging features of lipomatous tumors","volume":"10","author":"Baffour","year":"2020","journal-title":"Am. J. Nucl. Med. Mol. Imaging"},{"key":"ref_13","first-page":"535","article-title":"Establishment of a novel human dedifferentiated liposarcoma cell line, FU-DDLS-1: Conventional and molecular cytogenetic characterization","volume":"22","author":"Nishio","year":"2003","journal-title":"Int. J. Oncol."},{"key":"ref_14","first-page":"764","article-title":"Cytogenetic and molecular cytogenetic findings in giant dedifferentiated liposarcoma of the thigh","volume":"27","author":"Nishio","year":"2012","journal-title":"Oncol. Lett"},{"key":"ref_15","first-page":"345","article-title":"Immunohistochemical, cytogenetic, and molecular cytogenetic characterization of both components of a dedifferentiated liposarcoma: Implications for histogenesis","volume":"35","author":"Nishio","year":"2015","journal-title":"Anticancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Sciot, R. (2021). MDM2 Amplified Sarcomas: A Literature Review. Diagnostics, 11.","DOI":"10.3390\/diagnostics11030496"},{"key":"ref_17","first-page":"1835","article-title":"Characterization of the 12q amplicons in lipomatous soft tissue tumors by multiplex ligation-dependent probe amplification-based copy number analysis","volume":"35","author":"Creytens","year":"2015","journal-title":"Anticancer. Res."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2233","DOI":"10.1002\/ijc.23380","article-title":"HMGA2 is the partner of MDM2 in well-differentiated and dedifferentiated liposarcomas whereas CDK4 belongs to a distinct inconsistent amplicon","volume":"122","author":"Italiano","year":"2008","journal-title":"Int. J. Cancer"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"715","DOI":"10.1038\/ng.619","article-title":"Subtype-specific genomic alterations define new targets for soft-tissue sarcoma therapy","volume":"42","author":"Barretina","year":"2010","journal-title":"Nat. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"42429","DOI":"10.18632\/oncotarget.6464","article-title":"Genomic landscape of liposarcoma","volume":"6","author":"Kanojia","year":"2015","journal-title":"Oncotarget"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1200\/JCO.2017.74.9598","article-title":"Clinical and Molecular Spectrum of Liposarcoma","volume":"36","author":"Lee","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1002\/gcc.20835","article-title":"Evaluation of well-differentiated\/de-differentiated liposarcomas by high-resolution oligonucleotide array-based comparative genomic hybridization","volume":"50","author":"Tap","year":"2011","journal-title":"Genes Chromosomes Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.ccr.2007.02.007","article-title":"JUN oncogene amplification and overexpression block adipocytic differentiation in highly aggressive sarcomas","volume":"11","author":"Mariani","year":"2007","journal-title":"Cancer Cell"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1002\/gcc.20012","article-title":"ASK1(MAP3K5) as a potential therapeutic target in malignant fibrous histiocytomas with 12q14-q15 and 6q23 amplifications","volume":"40","author":"Chibon","year":"2004","journal-title":"Genes Chromosom. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"12941","DOI":"10.18632\/oncotarget.14652","article-title":"Frequent amplification of receptor tyrosine kinase genes in welldifferentiated\/dedifferentiated liposarcoma","volume":"8","author":"Asano","year":"2017","journal-title":"Oncotarget"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1053\/j.semdp.2019.02.003","article-title":"Molecular updates in adipocytic neoplasms","volume":"36","author":"Demicco","year":"2019","journal-title":"Semin. Diagn. Pathol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.cmet.2013.08.009","article-title":"The hypoxia-inducible microRNA cluster miR-199a~214 targets myocardial PPAR \u03b3 and impairs mitochondrial fatty acid oxidation","volume":"18","author":"Leptidis","year":"2013","journal-title":"Cell Metab."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1097\/PAS.0000000000000366","article-title":"Myogenic differentiation and histologic grading are major prognostic determinants in retroperitoneal liposarcoma","volume":"39","author":"Gronchi","year":"2015","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1097\/PAS.0000000000001436","article-title":"Prognostic Value of Myogenic differentiation in dedifferentiated liposarcoma","volume":"44","author":"Kurzawa","year":"2020","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_30","first-page":"E114","article-title":"Dedifferentiated liposarcoma of the thigh with chondrosarocomatous dedifferentiated component","volume":"39","author":"Yoon","year":"2010","journal-title":"Am. J. Orthop."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1097\/00000478-199808000-00004","article-title":"Dedifferentiated liposarcoma: A report of nine cases with a peculiar neurallike whorling pattern associated with metaplastic bone formation","volume":"22","author":"Nascimento","year":"1998","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"414","DOI":"10.1046\/j.1365-2559.1998.00536.x","article-title":"Liposarcoma with meningothelial-like whorls: A study of 17 cases of a distinctive histological pattern associated with dedifferentiated liposarcoma","volume":"33","author":"Miettinen","year":"1998","journal-title":"Histopathology"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1097\/01.pas.0000170343.09562.39","article-title":"MDM2 and CDK4 immunostainings are useful adjuncts in diagnosing well-differentiated and dedifferentiated liposarcoma subtypes: A comparative analysis of 559 soft tissue neoplasms with genetic data","volume":"29","author":"Binh","year":"2005","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.humpath.2016.08.009","article-title":"Differential diagnosis of atypical lipomatous tumor\/well-differentiated liposarcoma and dedifferentiated liposarcoma: Utility of p16 in combination with MDM2 and CDK4 immunohistochemistry","volume":"59","author":"Thierry","year":"2017","journal-title":"Hum. Pathol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"462","DOI":"10.1097\/PAS.0b013e3182417330","article-title":"Diagnostic Utility of p16, CDK4, and MDM2 as an Immunohistochemical Panel in Distinguishing Well-differentiated and Dedifferentiated Liposarcomas From Other Adipocytic Tumors","volume":"36","author":"Thway","year":"2012","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1097\/00000478-199702000-00009","article-title":"Immunoreactivity for the Human Hematopoietic Progenitor Cell Antigen (CD34) in Lipomatous Tumors","volume":"21","author":"Suster","year":"1997","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"943","DOI":"10.1038\/modpathol.2008.84","article-title":"Fluorescence in situ hybridization for MDM2 gene amplification as a diagnostic tool in lipomatous neoplasms","volume":"21","author":"Weaver","year":"2008","journal-title":"Mod. Pathol."},{"key":"ref_38","first-page":"1306","article-title":"Utility of fluorescence in situ hybridization to detect MDM2 amplification in liposarcomas and their morphological mimics","volume":"15","author":"Kimura","year":"2013","journal-title":"Int. J. Clin. Exp. Pathol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1476","DOI":"10.1097\/PAS.0b013e3180581fff","article-title":"Detection of MDM2-CDK4 amplification by fluorescence in situ hybridization in 200 paraffin-embedded tumor samples: Utility in diagnosing adipocytic lesions and comparison with immunohistochemistry and real-time PCR","volume":"31","author":"Sirvent","year":"2007","journal-title":"Am. J. Surg. Pathol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1158\/1078-0432.CCR-08-3185","article-title":"Clinical and biological significance of CDK4 amplification in well-differentiated and dedifferentiated liposarcomas","volume":"15","author":"Italiano","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1038\/modpathol.2014.88","article-title":"Prognostic relevance of F\u00e9d\u00e9ration Nationale des Centres de Lutte Contre le Cancer grade and MDM2 amplification levels in dedifferentiated liposarcoma: A study of 50 cases","volume":"28","author":"Jour","year":"2015","journal-title":"Mod. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/j.cancergen.2017.09.005","article-title":"High amplification levels of MDM2 and CDK4 correlate with poor outcome in patients with dedifferentiated liposarcoma: A cytogenomic microarray analysis of 47 cases","volume":"218\u2013219","author":"Ricciotti","year":"2017","journal-title":"Cancer Genet."},{"key":"ref_43","first-page":"127","article-title":"High level of CDK4 amplification is a poor prognostic factor in well-differentiated and dedifferentiated liposarcoma","volume":"29","author":"Lee","year":"2013","journal-title":"Histol. Histopathol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1200\/JCO.2008.17.8871","article-title":"Aggressive Surgical Policies in a Retrospectively Reviewed Single-Institution Case Series of Retroperitoneal Soft Tissue Sarcoma Patients","volume":"27","author":"Gronchi","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1016\/S1470-2045(16)30050-X","article-title":"Preoperative or postoperative radiotherapy versus surgery alone for retroperitoneal sarcoma: A case-control, propensity score-matched analysis of a nationwide clinical oncology database","volume":"17","author":"Nussbaum","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"1290","DOI":"10.1002\/cncr.31927","article-title":"Radiotherapy for retroperitoneal liposarcoma: A report from the Transatlantic Retroperitoneal Sarcoma Working Group","volume":"125","author":"Haas","year":"2019","journal-title":"Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1366","DOI":"10.1016\/S1470-2045(20)30446-0","article-title":"Preoperative radiotherapy plus surgery versus surgery alone for patients with primary retroperitoneal sarcoma (EORTC-62092: STRASS): A multicentre, open-label, randomized, phase 3 trial","volume":"21","author":"Bonvalot","year":"2020","journal-title":"Lancet Oncol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1080\/13577140020008066","article-title":"Doxorubicin-based chemotherapy for the palliative treatment of adult patients with locally advanced or metastatic soft-tissue sarcoma: A meta-analysis and clinical practice guideline","volume":"4","author":"Bramwell","year":"2000","journal-title":"Sarcoma"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1007\/s11864-020-0705-7","article-title":"Dedifferentiated liposarcoma: Systemic therapy options","volume":"21","author":"Gahvari","year":"2020","journal-title":"Curr. Treat. Options Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1016\/S1470-2045(14)70063-4","article-title":"Doxorubicin alone versus intensified doxorubicin plus ifosfamide for first-line treatment of advanced or metastatic soft-tissue sarcoma: A randomised controlled phase 3 trial","volume":"15","author":"Judson","year":"2014","journal-title":"Lancet Oncol."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"3898","DOI":"10.1200\/JCO.2016.67.6684","article-title":"PICASSO III: A Phase III, Placebo-Controlled Study of Doxorubicin With or Without Palifosfamide in Patients With Metastatic Soft Tissue Sarcoma","volume":"34","author":"Ryan","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1089","DOI":"10.1016\/S1470-2045(17)30381-9","article-title":"Doxorubicin plus evofosfamide versus doxorubicin alone in locally advanced, unresectable or metastatic soft-tissue sarcoma (TH CR-406\/SARC021): An international, multicentre, open-label, randomised phase 3 trial","volume":"18","author":"Tap","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1080\/0284186X.2017.1315173","article-title":"Predictive and prognostic factors associated with soft tissue sarcoma response to chemotherapy: A subgroup analysis of the European Organisation for Research and Treatment of Cancer 62012 study","volume":"56","author":"Young","year":"2017","journal-title":"Acta Oncol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"2853","DOI":"10.1016\/j.ejca.2005.07.023","article-title":"Differential sensitivity of liposarcoma subtypes to chemotherapy","volume":"41","author":"Jones","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"1601","DOI":"10.1093\/annonc\/mdr485","article-title":"Advanced well-differentiated\/dedifferentiated liposarcomas: Role of chemotherapy and survival","volume":"23","author":"Italiano","year":"2012","journal-title":"Ann. Oncol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11836","DOI":"10.1038\/s41598-017-12132-w","article-title":"Role of chemotherapy in dedifferentiated liposarcoma of the retroperitoneum: Defining the benefit and challenges of the standard","volume":"19","author":"Livingston","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3126","DOI":"10.1200\/JCO.2008.21.3223","article-title":"Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: A phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043)","volume":"27","author":"Sleijfer","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"1879","DOI":"10.1016\/S0140-6736(12)60651-5","article-title":"Pazopanib for metastatic soft-tissue sarcoma (PALETTE): A randomised, double-blind, placebo-controlled phase 3 trial","volume":"379","author":"Blay","year":"2012","journal-title":"Lancet"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"4640","DOI":"10.1002\/cncr.30926","article-title":"Results of a prospective phase 2 study of pazopanib in patients with advanced intermediate-grade or high-grade liposarcoma","volume":"123","author":"Samuels","year":"2017","journal-title":"Cancer"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"11039","DOI":"10.1200\/JCO.2016.34.15_suppl.11039","article-title":"Phase II clinical trial evaluating the activity and tolerability of pazopanib in patients (pts) with advanced and\/or metastatic liposarcoma (LPS): A joint Spanish Sarcoma Group (GEIS) and German Interdisciplinary Sarcoma Group (GISG) Study\u2014NCT01692496","volume":"34","author":"Valverde","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"11506","DOI":"10.1200\/JCO.2018.36.15_suppl.11506","article-title":"Randomized comparison of pazopanib (PAZ) and doxorubicin (DOX) in the first line treatment of metastatic soft tissue sarcoma (STS) in elderly patients (pts): Results of a phase II study (EPAZ)","volume":"36","author":"Kunitz","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2461","DOI":"10.1097\/CORR.0000000000001322","article-title":"Assessment of Predictive Biomarkers of the Response to Pazopanib Based on an Integrative Analysis of High-grade Soft-tissue Sarcomas: Analysis of a Tumor Sample from a Responder and Patients with Other Soft-tissue Sarcomas","volume":"478","author":"Suehara","year":"2020","journal-title":"Clin. Orthop. Relat. Res."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"1963","DOI":"10.1002\/ijc.25843","article-title":"Phase II study of sunitinib malate, a multitargeted tyrosine kinase inhibitor in patients with relapsed or refractory soft tissue sarcomas. Focus on three prevalent histologies: Leiomyosarcoma, liposarcoma and malignant fibrous histiocytoma","volume":"129","author":"Mahmood","year":"2011","journal-title":"Int. J. Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1732","DOI":"10.1016\/S1470-2045(16)30507-1","article-title":"Safety and efficacy of regorafenib in patients with advanced soft tissue sarcoma (REGOSARC): A randomised, double-blind, placebo-controlled, phase 2 trial","volume":"17","author":"Mir","year":"2016","journal-title":"Lancet Oncol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5233","DOI":"10.1158\/1078-0432.CCR-17-3766","article-title":"Safety and Efficacy of Anlotinib, a Multikinase Angiogenesis Inhibitor, in Patients with Refractory Metastatic Soft-Tissue Sarcoma","volume":"24","author":"Chi","year":"2018","journal-title":"Clin. Cancer Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1629","DOI":"10.1016\/S0140-6736(15)01283-0","article-title":"Eribulin versus dacarbazine in previously treated patients with advanced liposarcoma or leiomyosarcoma: A randomised, open-label, multicentre, phase 3 trial","volume":"387","author":"Chawla","year":"2016","journal-title":"Lancet"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3433","DOI":"10.1200\/JCO.2016.71.6605","article-title":"Activity of Eribulin in Patients With Advanced Liposarcoma Demonstrated in a Subgroup Analysis From a Randomized Phase III Study of Eribulin Versus Dacarbazine","volume":"35","author":"Demetri","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"786","DOI":"10.1200\/JCO.2015.62.4734","article-title":"Efficacy and Safety of Trabectedin or Dacarbazine for Metastatic Liposarcoma or Leiomyosarcoma After Failure of Conventional Chemotherapy: Results of a Phase III Randomized Multicenter Clinical Trial","volume":"34","author":"Demetri","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2610","DOI":"10.1002\/cncr.32117","article-title":"Overall survival and histology-specific subgroup analyses from a phase 3, randomized controlled study of trabectedin or dacarbazine in patients with advanced liposarcoma or leiomyosarcoma","volume":"125","author":"Patel","year":"2019","journal-title":"Cancer"},{"key":"ref_70","doi-asserted-by":"crossref","unstructured":"Fabbroni, C., Fuc\u00e0, G., Ligorio, F., Fumagalli, E., Barisella, M., Collini, P., Morosi, C., Gronchi, A., Dei Tos, A.P., and Casali, P.G. (2021). Impact of pathological stratification on the clinical outcomes of advanced well-differentiated\/dedifferentiated liposarcoma treated with trabectedin. Cancers, 13.","DOI":"10.3390\/cancers13061453"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"999","DOI":"10.1634\/theoncologist.12-8-999","article-title":"Gemcitabine and docetaxel in metastatic sarcoma: Past, present, and feature","volume":"12","author":"Maki","year":"2007","journal-title":"Oncologist"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1200\/JCO.2006.10.4117","article-title":"Randomized phase II study of gemcitabine and docetaxel compared with gemcitabine alone in patients with metastatic soft-tissue sarcomas","volume":"25","author":"Maki","year":"2007","journal-title":"J. Clin. Oncol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1397","DOI":"10.1016\/S1470-2045(17)30622-8","article-title":"Gemcitabine and docetaxel versus doxorubicin as first-line treatment in previously untreated advanced unresectable or metastatic soft-tissue sarcomas (GeDDiS): A randomised controlled phase 3 trial","volume":"18","author":"Seddon","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1158\/1078-0432.CCR-15-1522","article-title":"SAR405838: A Novel and Potent Inhibitor of the MDM2:p53 Axis for the Treatment of Dedifferentiated Liposarcoma","volume":"22","author":"Bill","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"1133","DOI":"10.1016\/S1470-2045(12)70474-6","article-title":"Effect of the MDM2 antagonist RG7112 on the P53 pathway in patients with MDM2-amplified, well-differentiated or dedifferentiated liposarcoma: An exploratory proof-of-mechanism study","volume":"13","author":"Blay","year":"2012","journal-title":"Lancet Oncol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"144","DOI":"10.1016\/j.ejca.2017.02.005","article-title":"A phase I study of SAR405838, a novel human double minute 2 (HDM2) antagonist, in patients with solid tumours","volume":"76","author":"Dickson","year":"2017","journal-title":"Eur. J. Cancer"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1304","DOI":"10.1200\/JCO.2016.70.7117","article-title":"Phase I Trial of the Human Double Minute 2 Inhibitor MK-8242 in Patients With Advanced Solid Tumors","volume":"35","author":"Wagner","year":"2017","journal-title":"J. Clin. Oncol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"11514","DOI":"10.1200\/JCO.2018.36.15_suppl.11514","article-title":"A phase 1 study of MDM2 inhibitor DS-3032b in patients with well\/de-differentiated liposarcoma (WD\/DD LPS), solid tumors (ST) and lymphomas (L)","volume":"36","author":"Bauer","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12609","DOI":"10.1038\/ncomms12609","article-title":"TP53 mutations emerge with HDM2 inhibitor SAR405838 treatment in de-differentiated liposarcoma","volume":"7","author":"Jung","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1001\/jamaoncol.2016.0264","article-title":"Progression-free survival among patients with well-differentiated or dedifferentiated liposarcoma treated with CDK4 inhibitor palbociclib: A phase 2 clinical trial","volume":"2","author":"Dickson","year":"2016","journal-title":"JAMA Oncol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"5696","DOI":"10.1158\/1078-0432.CCR-16-1248","article-title":"A phase I study of the cyclin-dependent kinase 4\/6 inhibitor ribociclib (LEE011) in patients with advanced solid tumors and lymphomas","volume":"22","author":"Infante","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"11004","DOI":"10.1200\/JCO.2019.37.15_suppl.11004","article-title":"Phase 2 study of the CDK4 inhibitor abemaciclib in dedifferentiated liposarcoma","volume":"37","author":"Dickson","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1186\/s13045-017-0482-3","article-title":"Combined targeting of MDM2 and CDK4 is synergistic in dedifferentiated liposarcomas","volume":"10","author":"Chaire","year":"2017","journal-title":"J. Hematol. Oncol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"7521","DOI":"10.18632\/oncotarget.13485","article-title":"Molecular mechanism and therapeutic implications of selinexor (KPT-330) in liposarcoma","volume":"8","author":"Garg","year":"2017","journal-title":"Oncotarget"},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"83","DOI":"10.1186\/s13046-021-01886-x","article-title":"Selinexor versus doxorubicin in dedifferentiated liposarcoma PDXs: Evidence of greater activity and apoptotic response dependent on p53 nuclear accumulation and surviving down-regulation","volume":"40","author":"Zuco","year":"2021","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"3166","DOI":"10.1200\/JCO.2016.67.6346","article-title":"Phase IB Study of Selinexor, a First-in-Class Inhibitor of Nuclear Export, in Patients With Advanced Refractory Bone or Soft Tissue Sarcoma","volume":"34","author":"Gounder","year":"2016","journal-title":"J. Clin. Oncol."},{"key":"ref_87","unstructured":"Gounder, M., Razak, A.A., Somaiah, N., Martin-Broto, J., Schuetze, S., Grignani, G., Chawla, S.P., Chmielowski, B., Vincenzi, B., and Stacchiotti, S. (2020, January 18\u201321). A phase 2\/3, randomized, double-Blind, cross-over study of selinexor versus placebo in advanced unresectable dedifferentiated liposarcoma (DDLS). Proceedings of the Connective Tissue Oncology Society (CTOS) Virtual Annual Meeting, Online."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Gounder, M., Razak, A.R.A., Gilligan, A.M., Leong, H., Ma, X., Somaiah, N., Chawla, S.P., Martin-Broto, J., Grignani, G., and Schuetze, S.M. (2021). Health-related quality of life and pain with selinexor in patients with advanced dedifferentiated liposarcoma. Futur. Oncol.","DOI":"10.2217\/fon-2021-0284"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"3819","DOI":"10.1002\/cncr.31517","article-title":"Rationale and emerging strategies for immune checkpoint blockade in soft tissue sarcoma","volume":"124","author":"Wisdom","year":"2018","journal-title":"Cancer"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1186\/s12967-018-1658-5","article-title":"Status of programmed death-ligand 1 expression in sarcomas","volume":"16","author":"Park","year":"2018","journal-title":"J. Transl. Med."},{"key":"ref_91","doi-asserted-by":"crossref","unstructured":"Vargas, A.C., MacLean, F.M., Sioson, L., Tran, D., Bonar, F., Mahar, A., Cheah, A.L., Russell, P., Grimison, P., and Richardson, L. (2020). Prevalence of PD-L1 expression in matched recurrent and\/or metastatic sarcoma samples and in a range of selected sarcomas subtypes. PLoS ONE, 15.","DOI":"10.1371\/journal.pone.0222551"},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3892\/ol.2020.12052","article-title":"Integrative assessment of clinicopathological parameters and the expression of PD-L1, PD-L2 and PD-1 in tumor cells of retroperitoneal sarcoma","volume":"20","author":"Miyake","year":"2020","journal-title":"Oncol. Lett."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"1493","DOI":"10.1016\/S1470-2045(17)30624-1","article-title":"Pembrolizumab in advanced soft-tissue sarcoma and bone sarcoma (SARC028): A multicentre, two-cohort, single-arm, open-label, phase 2 trial","volume":"18","author":"Burgess","year":"2017","journal-title":"Lancet Oncol."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"11015","DOI":"10.1200\/JCO.2019.37.15_suppl.11015","article-title":"Clinical activity of pembrolizumab (P) in undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated\/pleomorphic liposarcoma (LPS): Final results of SARC028 expansion cohorts","volume":"37","author":"Burgess","year":"2019","journal-title":"J. Clin. Oncol."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/S1470-2045(18)30006-8","article-title":"Nivolumab with or without ipilimumab treatment for metastatic sarcoma (Alliance A091401): Two open-label, non-comparative, randomised, phase 2 trials","volume":"19","author":"Mahoney","year":"2018","journal-title":"Lancet Oncol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"11511","DOI":"10.1200\/JCO.2020.38.15_suppl.11511","article-title":"A multicenter phase II study of nivolumab +\/\u2212 ipilimumab for patients with metastatic sarcoma (Alliance A091401): Results of expansion cohorts","volume":"38","author":"Chen","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_97","doi-asserted-by":"crossref","unstructured":"Keung, E.Z., Lazar, A.J., E Torres, K., Wang, W.-L., Cormier, J.N., Guadagnolo, B.A., Bishop, A., Lin, H., Hunt, K.K., and Bird, J. (2018). Phase II study of neoadjuvant checkpoint blockade in patients with surgically resectable undifferentiated pleomorphic sarcoma and dedifferentiated liposarcoma. BMC Cancer, 18.","DOI":"10.1186\/s12885-018-4829-0"},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"11505","DOI":"10.1200\/JCO.2020.38.15_suppl.11505","article-title":"Preliminary results of a phase II study of neoadjuvant checkpoint blockade for surgically resectable undifferentiated pleomorphic sarcoma (UPS) and dedifferentiated liposarcoma (DDLPS)","volume":"38","author":"Roland","year":"2020","journal-title":"J. Clin. Oncol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"11588","DOI":"10.1200\/JCO.2018.36.15_suppl.TPS11588","article-title":"SU2C-SARC032: A phase II randomized controlled trial of neoadjuvant pembrolizumab with radiotherapy and adjuvant pembrolizumab for high-risk soft tissue sarcoma","volume":"36","author":"Mowery","year":"2018","journal-title":"J. Clin. Oncol."}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3230\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:33:18Z","timestamp":1760164398000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,22]]},"references-count":99,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["jcm10153230"],"URL":"https:\/\/doi.org\/10.3390\/jcm10153230","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,22]]}}}