Lee JY, et al. - Researchers focused on the potential role of MEL-18, a polycomb group gene, as a novel prognostic marker for trastuzumab resistance in HER2-positive (HER2+) breast cancer, given that resistance to HER2-targeted therapy with trastuzumab still remains a major challenge in HER2-amplified tumors. They examined multiple breast cancer cohorts, including METABRIC (n=1,980), TCGA (n=825), and clinical specimens (n=213, trastuzumab-treated HER2+ cases), to assess the genetic alteration of MEL-18 and its clinical relevance. Findings suggested MEL-18 amplification as a novel biomarker for HER2+ breast cancer as researchers found that MEL-18 served to prevent ligand-dependent ErbB heterodimerization and trastuzumab resistance.