Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies

摘要: A chromosomal region that includes the gene encoding HER2, a receptor tyrosine kinase (RTK), is amplified in 20% of breast cancers. Although these tumors tend to respond drugs directed against they frequently become resistant and resume their malignant progression. Gene amplification double minutes (DMs), which are extrachromosomal entities whose number can be dynamically regulated, has been suggested facilitate acquisition resistance therapies targeting RTKs. Here we show ~30% HER2-positive DMs. However, trastuzumab similar fashion than those with HER2 within chromosomes. Furthermore, different models anti-HER2 therapies, DMs containing maintained, even when concomitant loss protein expression. Thus, both clinical preclinical data that, despite expectations, expression due not likely mechanism therapies.