Summary
Osteosarcoma (OS) is the most common primary aggressive and malignant bone tumor. Newly diagnostic OS patients benefit from the standard therapy including surgical resection plus radiotherapy and neoadjuvant chemotherapy (MAP chemotherapy: high-dose methotrexate, doxorubicin and cisplatin). However, tumor recurrence and metastasis give rise to a sharp decline of the 5-year overall survival rate in OS patients. Little improvement has been made for decades, urging the development of more effective therapeutic approaches. ErbB receptor family including EGFR, HER2, HER3 and HER4, being important to the activation of PI3K/Akt and MAPK signaling pathways, are potential targets for OS treatment. Genetic aberrations (amplification, overexpression, mutation and altered splicing) of ErbB are essential to the growth, apoptosis, motility and metastasis in a variety of cancers. Overexpression of ErbB family is associated with the poor prognosis of cancer patients. A number of monoclonal antibodies or inhibitors specific for ErbB family have entered clinical trials in a range of solid tumors including breast carcinoma, lung carcinoma and sarcoma. Here, we summarized the roles and expression of ErbB family in OS and the current development of ErbB-targeted therapeutic strategies including chemotherapies and immunotherapies for OS treatment.
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Abbreviations
- ADCC:
-
Antibody-dependent cell-mediated cytotoxicity
- ATP:
-
Adenosine triphosphate
- CAR:
-
Chimeric antigen receptor
- CAR-T:
-
Chimeric antigen receptor T cell immunotherapy
- DAC:
-
5-aza-2′-deoxycytidine
- DLT:
-
Dose-limiting toxicity
- EGF:
-
Epidermal growth factor
- EGFR:
-
Epidermal growth factor receptor
- ERα:
-
Estrogen receptor α
- H&N:
-
Head and neck cancer
- HB-EGF:
-
Heparin-binding EGF
- HRG:
-
Heregulin
- IFNγ:
-
Interferon γ
- IGF:
-
Insulin like growth factor
- IGF-IR:
-
Insulin-like growth factor I receptor
- IL:
-
Interleukin
- JM:
-
Juxtamembrane
- MAPK:
-
Mitogen-activated protein kinase
- MTD:
-
Maximum-tolerated dose
- NK:
-
Natural killer
- NSCLC:
-
Non-small cell lung cancer
- NRG:
-
Neuregulin
- OS:
-
Osteosarcoma
- PEA:
-
Pseudomonas exotoxin A
- PFS:
-
Progression-free survival
- PI3K:
-
Phosphatidylinositol 3-kinase
- ROS:
-
Reactive oxygen species
- RTK:
-
Receptor tyrosine kinase
- SH2:
-
Src homology 2
- TACE:
-
Tumor necrosis factor-α-converting enzyme
- TGFα:
-
Transforming growth factor α
- TIC:
-
Tumor-initiating cell
- VEGFR:
-
Vascular endothelial growth factor receptor.
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The authors would like to thank Qing-shui Yin for the discussion of the manuscript.
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This work was supported by Grants from National Natural Science Foundation of China (No. 81602195), Natural Science Foundation of Guangdong Province (No.2017A030313531), Shenzhen Science and Technology Innovation Commission (No. JCYJ20160425104157183).
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Wang, W., Zhao, Hf., Yao, Tf. et al. Advanced development of ErbB family-targeted therapies in osteosarcoma treatment. Invest New Drugs 37, 175–183 (2019). https://doi.org/10.1007/s10637-018-0684-8
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DOI: https://doi.org/10.1007/s10637-018-0684-8