Glycogen synthase kinase 3b biology in bone and soft tissue sarcomas  

作　　者：Kensaku Abe Shingo Shimozaki Takahiro Domoto Norio Yamamoto Hiroyuki Tsuchiya Toshinari Minamoto 

机构地区：[1]Department of Orthopaedic Surgery,Graduate School of Medical Sciences,Kanazawa University,Kanazawa 920-8641,Japan [2]Division of Translational and Clinical Oncology,Cancer Research Institute,Kanazawa University,Kanazawa 920-0934,Japan [3]Shimozaki Orthopaedic Hospital,Hakusan,Ishikawa 924-0802,Japan

出　　处：《Journal of Cancer Metastasis and Treatment》2020年第1期660-674,共15页癌症转移与治疗（英文版）

基　　金：Grants-in-Aid for Scientific Research from the Ministry of Education,Culture,Sports,Science and Technology-Japan and from the Japan Society for the Promotion of Science(to Abe K,Yamamoto N,Tsuchiya H,and Minamoto T).

摘　　要：Bone and soft tissue sarcomas are malignant neoplasms probably originating from musculoskeletal and mesenchymal progenitor cells.More than 80 different histopathological subtypes are encountered in orthopedics.The standard of care for sarcoma patients involves a multidisciplinary combination of surgery,anthracycline-based multiagent chemotherapy and radiation.Unfortunately,these are associated with adverse events and occasionally disappointing outcomes.Various genomic-,biologically-,and immunologically-based therapies are still under evaluation in early-phase clinical trials.However,there are strong barriers to the development and clinical translation of new therapeutic modalities.This is due to the rarity of these diseases,the broad spectrum of tumor subtypes with genetic and biological heterogeneity,and the wide variability in clinical manifestation,response to treatment and prognosis.A potential approach toward overcoming this barrier is to identify therapeutic targets that cover multiple sarcoma types.Glycogen synthase kinase 3b(GSK3b)has emerged as a common therapeutic target in more than 25 different cancer types.Here we review the evidence for tumor-promoting roles of GSK3b in the major types of bone and soft tissue sarcomas including osteosarcoma,rhabdomyosarcoma,synovial sarcoma,and fibrosarcoma.In this review,we describe the therapeutic effects of inhibiting GSK3b in these sarcoma types,while also protecting healthy cells and tissues from detrimental effects associated with conventional therapies,such as doxorubicin-induced cardiotoxicity.Consequently,we highlight GSK3b as a potential therapeutic target spanning multiple sarcoma types.

关 键 词：OSTEOSARCOMA RHABDOMYOSARCOMA synovial sarcoma FIBROSARCOMA glycogen synthase kinase 3b 

分 类 号：R73[医药卫生—肿瘤]