Advanced development of ErbB family-targeted therapies in osteosarcoma treatment

• Published in: Investigational new drugs Vol. 37; no. 1; pp. 175 - 183
• Main Authors: Wang, Wei, Zhao, Hua-fu, Yao, Teng-fei, Gong, Hao
• Format: Journal Article
• Language: English
• Published: New York Springer US 01.02.2019; Springer Nature B.V
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Apoptosis; Biocompatibility; Bone cancer; Bone Neoplasms - drug therapy; Bone Neoplasms - metabolism; Bone Neoplasms - pathology; Bone tumors; Breast cancer; Breast carcinoma; Chemotherapy; Cisplatin; Clinical trials; Diagnostic systems; Doxorubicin; Epidermal growth factor receptors; ErbB protein; ErbB Receptors - antagonists & inhibitors; ErbB-2 protein; Humans; Immunotherapy; Lung carcinoma; MAP kinase; Medical prognosis; Medical research; Medicine; Medicine & Public Health; Metastases; Metastasis; Methotrexate; Molecular Targeted Therapy; Monoclonal antibodies; Oncology; Osteosarcoma; Osteosarcoma - drug therapy; Osteosarcoma - metabolism; Osteosarcoma - pathology; Patients; Pharmacology/Toxicology; Prognosis; Radiation therapy; Review; Sarcoma; Solid tumors; Splicing; Surgery; Tumors; Metastasis; ErbB; Osteosarcoma; Immunotherapy
• ISSN: 0167-6997; 1573-0646
• DOI: 10.1007/s10637-018-0684-8

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.