Changes in the ECM enhance tumor cell invasion and metastasis while also affecting the overall immune response in the TME, complicating treatment strategies.141 For example, targeting the hexosamine biosynthesis pathway (HBP) in pancreatic ductal adenocarcinoma (PDAC) by inhibiting the glutamine-utilizing enzyme GFAT1 with the small-molecule glutamine analog DON effectively reduces tumor self-renewal and metastatic potential. The gene discussed is GFPT1; the disease is neoplasm.