Scientists identify metabolic pathway driving cetuximab resistance

◇ RESEARCH

Scientists identify metabolic pathway driving cetuximab resistance — Cell Death & Disease

Researchers discovered that glutamate dehydrogenase 1 (GDH1) accumulation drives cetuximab resistance in metastatic colorectal cancer. When cetuximab blocks EGFR, it prevents phosphorylation of GDH1, leading to its accumulation and increased production of α-ketoglutarate (αKG). This metabolic change remodels the tumor immune microenvironment to suppress immune responses. GDH1 depletion sensitized CRC cells to cetuximab and suppressed remodeling of the tumor immune microenvironment, as revealed by single-cell RNA sequencing.