Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma

Osteosarcoma (OS), frequently observed in children and adolescents, is one of the most common primary malignant tumors of the bone known to be associated with a high capacity for invasion and metastasis. The incidence of osteosarcoma in children and adolescents is growing annually, although improvem...

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Main Authors: Xianglin Peng, Jing Feng, Han Yang, Ping Xia, Feifei Pu
Format: Article
Language:English
Published: KeAi Communications Co., Ltd. 2025-07-01
Series:Genes and Diseases
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Online Access:http://www.sciencedirect.com/science/article/pii/S2352304224001326
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author Xianglin Peng
Jing Feng
Han Yang
Ping Xia
Feifei Pu
author_facet Xianglin Peng
Jing Feng
Han Yang
Ping Xia
Feifei Pu
author_sort Xianglin Peng
collection DOAJ
description Osteosarcoma (OS), frequently observed in children and adolescents, is one of the most common primary malignant tumors of the bone known to be associated with a high capacity for invasion and metastasis. The incidence of osteosarcoma in children and adolescents is growing annually, although improvements in survival remain limited. With the clinical application of neoadjuvant chemotherapy, chemotherapy combined with limb-preserving surgery has gained momentum as a major intervention. However, certain patients with OS experience treatment failure owing to chemoradiotherapy resistance or metastasis. Nuclear factor E2-related factor 2 (Nrf2), a key antioxidant factor in organisms, plays a crucial role in maintaining cellular physiological homeostasis; however, its overactivation in cancer cells restricts reactive oxygen species production, promotes DNA repair and drug efflux, and ultimately leads to chemoradiotherapy resistance. Recent studies have also identified the functions of Nrf2 beyond its antioxidative function, including the promotion of proliferation, metastasis, and regulation of metabolism. The current review describes the multiple mechanisms of chemoradiotherapy resistance in OS and the substantial role of Nrf2 in the signaling regulatory network to elucidate the function of Nrf2 in promoting OS chemoradiotherapy resistance and formulating relevant therapeutic strategies.
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spelling doaj-art-cd07e9b9f92d4e66a7f647efbf1e563d2025-08-20T03:11:06ZengKeAi Communications Co., Ltd.Genes and Diseases2352-30422025-07-0112410133510.1016/j.gendis.2024.101335Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcomaXianglin Peng0Jing Feng1Han Yang2Ping Xia3Feifei Pu4Department of Orthopedics, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Orthopedics, Wuhan No.1 Hospital, Wuhan 430022, ChinaDepartment of Orthopedics, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Orthopedics, Wuhan No.1 Hospital, Wuhan 430022, ChinaSpecial Key Laboratory of Gene Detection and Therapy of Guizhou Province, Zunyi Medical University, Zunyi 563000, China; Department of Immunology, Zunyi Medical University, Zunyi 563000, ChinaDepartment of Orthopedics, Wuhan Fourth Hospital, Wuhan 430030, China; Corresponding author.Department of Orthopedics, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China; Department of Orthopedics, Wuhan No.1 Hospital, Wuhan 430022, China; Corresponding author. Department of Orthopedics, Wuhan Hospital of Traditional Chinese and Western Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China.Osteosarcoma (OS), frequently observed in children and adolescents, is one of the most common primary malignant tumors of the bone known to be associated with a high capacity for invasion and metastasis. The incidence of osteosarcoma in children and adolescents is growing annually, although improvements in survival remain limited. With the clinical application of neoadjuvant chemotherapy, chemotherapy combined with limb-preserving surgery has gained momentum as a major intervention. However, certain patients with OS experience treatment failure owing to chemoradiotherapy resistance or metastasis. Nuclear factor E2-related factor 2 (Nrf2), a key antioxidant factor in organisms, plays a crucial role in maintaining cellular physiological homeostasis; however, its overactivation in cancer cells restricts reactive oxygen species production, promotes DNA repair and drug efflux, and ultimately leads to chemoradiotherapy resistance. Recent studies have also identified the functions of Nrf2 beyond its antioxidative function, including the promotion of proliferation, metastasis, and regulation of metabolism. The current review describes the multiple mechanisms of chemoradiotherapy resistance in OS and the substantial role of Nrf2 in the signaling regulatory network to elucidate the function of Nrf2 in promoting OS chemoradiotherapy resistance and formulating relevant therapeutic strategies.http://www.sciencedirect.com/science/article/pii/S2352304224001326CarcinogenesisNrf2OsteosarcomaResistanceTherapeutic strategies
spellingShingle Xianglin Peng
Jing Feng
Han Yang
Ping Xia
Feifei Pu
Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma
Genes and Diseases
Carcinogenesis
Nrf2
Osteosarcoma
Resistance
Therapeutic strategies
title Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma
title_full Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma
title_fullStr Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma
title_full_unstemmed Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma
title_short Nrf2: A key regulator in chemoradiotherapy resistance of osteosarcoma
title_sort nrf2 a key regulator in chemoradiotherapy resistance of osteosarcoma
topic Carcinogenesis
Nrf2
Osteosarcoma
Resistance
Therapeutic strategies
url http://www.sciencedirect.com/science/article/pii/S2352304224001326
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AT pingxia nrf2akeyregulatorinchemoradiotherapyresistanceofosteosarcoma
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