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Advanced development of ErbB family-targeted therapies in osteosarcoma treatment

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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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Acknowledgements

The authors would like to thank Qing-shui Yin for the discussion of the manuscript.

Availability of data and materials

Not applicable.

Funding

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).

Author information

Author notes

  1. Wei Wang and Hua-fu Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Orthopaedics, the First Affiliated Hospital of Jiangxi Medical College, Shangrao, 334000, China

    Wei Wang, Teng-fei Yao & Hao Gong

  2. Institute of Translational Medicine, Department of Neurosurgery and Shenzhen Key Laboratory of Neurosurgery, Shenzhen Second People’s Hospital, the First Affiliated Hospital of Shenzhen University, Shenzhen, 518035, China

    Hua-fu Zhao

Authors
  1. Wei Wang
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  2. Hua-fu Zhao
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  3. Teng-fei Yao
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  4. Hao Gong
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Correspondence to Wei Wang.

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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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