In particular, hypoxia within the TME of gastroenteropancreatic NETs (GEP-NETs) has been shown to induce promoter hypermethylation-mediated downregulation of carbonyl reductase 4 (CBR4), thereby promoting tumor progression through an ubiquitin-dependent reduction in fatty acid synthase (FASN) expression and the activation of the mTOR signaling pathway [84]. Here, CBR4 is linked to neoplasm.