Development of a test that measures real-time HER2 signaling function in live breast cancer cell lines and primary cells.

摘要: Approximately 18–20% of all human breast cancers have overexpressed epidermal growth factor receptor 2 (HER2). Standard clinical practice is to treat only HER2 (HER2+) with targeted anti-HER2 therapies. However, recent analyses trial data found evidence that HER2-targeted therapies may benefit a sub-group cancer patients non-overexpressed HER2. This suggests measurement other biological factors associated cancer, such as signaling pathway activity, should be considered an alternative means identifying eligible for A new biosensor-based test (CELxTM HSF) measures activity in live cells demonstrated using set 19 HER2+ and HER2– reference cell lines primary samples derived from two fresh patient tumor specimens. Pathway elucidated by use highly specific agonists antagonists. The method relies upon well-established phenotypic, adhesion-related, impedance changes detected the biosensor. analytical sensitivity analyte specificity this was ligands high affinity HER1 HER3. HER2-driven quantified ranged 50-fold between lowest highest lines. were almost equally divided into low result groups, suggesting little correlation exists protein expression level. Unexpectedly, level recorded line. Measurement feasible approach explore biomarker identify not currently diagnosable genomic techniques. wide range levels measured it possible make distinction normal abnormal activity. Analytical validation studies trials treating HER2- would required evaluate validity functional diagnostic select treatment therapy. In practice, require specimens delivered tested central lab.