title: Role of epigenetic modulation for the treatment of sarcoma.
abstract: Sarcoma is a disease that includes many different subtypes that can present with a wide range of differing clinical findings, prognosis, and treatment options. For certain subsets (e.g., Ewing sarcoma, osteosarcoma, rhabdomyosarcoma, gastrointestinal stromal tumor [GIST]), extensive clinical trials have delineated effective treatment regimens often involving combination therapy, including surgery, radiation, systemic chemotherapy, and small molecular inhibitors of tyrosine kinases (as in the case of GIST). For nearly all patients with sarcoma who have relapsed or developed metastasis, the therapeutic benefit of chemotherapy has reached a plateau and as such new treatment approaches are needed to move this field forward. We recommend that all patients have the opportunity to participate in clinical trials where available. Recently, in our clinic we have started to increase our use of molecular testing and DNA sequencing studies to help identify potential treatment options for patients. One area of evolving basic and clinical research in sarcomas is the field of epigenetic therapeutics. The enclosed article reviews the basics of epigenetics and highlights some completed and ongoing clinical trials of epigenetic treatments in sarcoma. We anticipate in the future that diagnostic platforms will be developed to help clinicians determine if an epigenetic therapy could be effective for an individual patient with sarcoma.
authors.affiliation: , 32 Fruit Street, Yawkey 7A, Boston, MA, 02114, USA, gcote@partners.org.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Cote
authors.forename: Edwin
authors.initials: E
authors.lastname: Choy
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols; D002986:Clinical Trials as Topic; D003131:Combined Modality Therapy; D000071221:Enhancer of Zeste Homolog 2 Protein; D044127:Epigenesis, Genetic / Q000235:genetics*; D006801:Humans; D063151:Polycomb Repressive Complex 2 / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics*; D012509:Sarcoma / Q000235:genetics / Q000473:pathology / Q000628:therapy*; D012512:Sarcoma, Ewing / Q000235:genetics* / Q000473:pathology / Q000628:therapy; D017422:Sequence Analysis, DNA
chemical_list: D047428:Protein Kinase Inhibitors; C498409:EZH2 protein, human; D000071221:Enhancer of Zeste Homolog 2 Protein; D063151:Polycomb Repressive Complex 2; D011505:Protein-Tyrosine Kinases