p95HER2 and Breast Cancer
Keywords:
p95HER2, epidermal growth factor receptor, breast cancerAbstract
Human epidermal growth factor receptor 2 (HER2) is a member of the epidermal growth factor receptor family of tyrosine kinases, and plays a significant role in a variety of cancers. HER2-positive breast-cancer patients have a poor prognosis, and HER2 can predict the response to anti-HER2 therapy among breast-cancer patients. HER2-positive breast cancers are currently treated with trastuzumab, monoclonal antibodies against the extracellular domain of the HER2 receptor, and small molecules that inhibit the intracellular kinase domain (e.g., lapatinib, neratinib, and afatinib). However, many patients are resistant to the HER2 monoclonal antibody, trastuzumab. It has been found that p95HER2 is a subgroup of HER2 protein with kinase activity and is associated with negative prognostic factors, including positive nodal status, shorter progressive free survival, or overall survival, in HER2-positive breast cancer. p95HER2 is likely a determinant of trastuzumab resistance, because it lacks the HER2 extracellular domain which is the binding site for trastuzumab. Identification of a subgroup with high p95HER2 expression may be useful in guiding treatment decisions for patients with HER2-positive breast cancer. Although p95HER2 confers trastuzumab resistance, it retains the HER2 tyrosine kinase domain and is sensitive to kinase inhibitors. However, some results showed that tumors expressing p95HER2 responded to trastuzumab plus chemotherapy.
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