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Abe et al. J Cancer Metastasis Treat 2020;6:51 Journal of Cancer
DOI: 10.20517/2394-4722.2020.117 Metastasis and Treatment

Review Open Access

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

Kensaku Abe 1,2,# , Shingo Shimozaki 1,2,3,# , Takahiro Domoto , Norio Yamamoto , Hiroyuki Tsuchiya ,
2
1
1
Toshinari Minamoto 2
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.
# Authors contributed equally.
Correspondence to: Dr. Toshinari Minamoto, Division of Translational and Clinical Oncology, Cancer Research Institute,
Kanazawa University, 13-1 Takara-machi, Kanazawa 920-0934, Japan. E-mail: minamoto@staff.kanazawa-u.ac.jp

How to cite this article: Abe K, Shimozaki S, Domoto T, Yamamoto N, Tsuchiya H, Minamoto T. Glycogen synthase kinase 3b
biology in bone and soft tissue sarcomas. J Cancer Metastasis Treat 2020;6:51. http://dx.doi.org/10.20517/2394-4722.2020.117

Received: 28 Oct 2020 Accepted: 27 Nov 2020 Published: 17 Dec 2020

Academic Editor: Ivory Ma, Ian Judson Copy Editor: Whitney Xu Production Editor: Jing Yu

Abstract
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.

Keywords: Osteosarcoma, rhabdomyosarcoma, synovial sarcoma, fibrosarcoma, glycogen synthase kinase 3b

© The Author(s) 2020. Open Access This article is licensed under a Creative Commons Attribution 4.0
International License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use,
sharing, adaptation, distribution and reproduction in any medium or format, for any purpose, even commercially, as long
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