Comprehensive molecular profiling of 5,175 esophagogastric cancer (EGC) patients identified distinct molecular signatures for early-onset (< 50 years of age, EOEGC, n=530) versus average-onset (AOEGC, n=4,645) tumors.
EOEGC has increased frequency of CDH1 mutations, ARHGAP26 fusions, enrichment of epithelial mesenchymal transition (EMT) and angiogenesis pathways, decreased MAPK pathway activity, decreased frequency of TMB-high and dMMR/MSI-H, and a unique immune cell infiltrate with decreased M1 macrophages and increased M2 macrophages.
These unique differential characteristics present therapeutic opportunities but also demonstrate the limitations of currently approved therapies in this subset of patients.
Abstract Objective Cervical cancer is caused by human papillomavirus (HPV) infections; however, there are no molecularly defined subtypes, and few approved targeted therapies. We defined molecular… […]
Mechanisms of resistance to trastuzumab deruxtecan in breast cancer elucidated by multi-omic molecular profiling
Abstract Trastuzumab deruxtecan (T-DXd) is an antibody-drug conjugate successfully used to treat HER2-low and HER2-positive metastatic breast cancer, but resistance consistently develops. Using multivariate Cox… […]