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Archive > Volume 23 Issue 4 > 2016,23(4):453-467. DOI:10.3872/j.issn.1007-385X.2016.04.001 Prev Next
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Mechanism of trastuzumab resistance and strategies to overcome the resistance
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Abstract:
Trastuzumab is a humanized monoclonal antibody targeting human epidermal growth factor receptor 2(HER2), which combined with chemotherapy drugs could significantly improve progression-free survival of patients. However, primary and acquired resistances of trastuzumab severely limit its curative effect and clinical application. Aberrant activation of PI3K/AKT/mTOR signaling pathway, interaction of HER family members, activation of compensatory survival signals under drug pressure and formation of phenotypes of cancer stem cells could be important mechanisms of the trastuzumab resistance. With deepening of research on mechanisms of trastuzumab resistance, treatments for overcoming trastuzumab resistance is also increasing. Some studies have shown that combination of trastuzumab with another monoclonal antibodies targeting HER2 extracellular domain or other HER family members could increase curative effect of trastuzumab. Application of small-molecule inhibitor of PI3K/AKT/mTOR signaling pathway or specific inhibitors of pro-survival signaling pathway that related to trastuzumab resisitance could effectively reverse the resistance and prolong progression-free survival of patients. In-depth researches on mechanisms of trastuzumab resistance and constant exploration on treatment strategies to reverse the resistance could provide the basis for establishment of individualized treatment plan of breast carcinoma.
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Project Supported:
Project supported by the National Key Technologies R&D Program for New Drugs (No.2013ZX09102056), the National High-Tech R&D Program of China (863 Program) (No. 2014AA020604), the National Natural Science Foundation of China (No. 31370825, 81272232, 81402562, 81572845, 81401311, 31500702), the National Postdoctoral Science Foundation of China (No. 2015T81095), and the Beijing Natural Science Foundation of China (No. 7122124, 7132163)
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