Abstract
HER2 is a tyrosine kinase receptor whose overexpression in breast cancers correlates with poor prognosis. A subset of HER2-positive tumors also expresses a series of HER2 fragments, collectively known as p95HER2. These fragments are emerging as a valuable biomarker for this subset of patients, who have a particularly poor prognosis.
Highlights
In this issue of Clinical Cancer Research, Sperinde and colleagues [1] report the generation and characterization of a monoclonal antibody that recognizes one of the p95HER2 carboxy-terminal fragments of HER2
Two types of agents are currently available for targeted treatment of HER2-positive tumors: monoclonal antibodies against the extracellular domain of HER2 and small molecule tyrosine kinase inhibitors
The p95HER2 status might become a decisive factor when choosing between different therapeutic regimens, because p95HER2-postive tumors are resistant to trastuzumab [4] but respond to lapatinib at least as effectively as p95HER2-negative tumors [5]
Summary
In this issue of Clinical Cancer Research, Sperinde and colleagues [1] report the generation and characterization of a monoclonal antibody that recognizes one of the p95HER2 carboxy-terminal fragments of HER2. The only difference between the 95 to 100 and the 100 to 115 kDa fragments, a stretch of approximately 30 amino acids, makes a remarkable difference This small region contains several cysteine residues that support constitutive homodimerization and, hyperactivation of the fragment generated by alternative initiation of translation The anti-p95HER2 assay was used on formalin-fixed, paraffin-embedded samples from a cohort of patients with metastatic breast cancer treated with trastuzumab They found that most of the HER2-positive tumors (approximately 80%) expressed detectable levels of p95HER2, the range of expression was wide (1- to 20-fold relative to negative controls). The assay developed by Sperinde and colleagues [1] only detects the hyperactive 100 to 115 kDa. p95HER2 fragment generated by initiation of translation from methionine 611 (Fig. 1) or larger fragments. As shown by Sperinde and colleagues [1], patients with high-p95HER2 tumors
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
