SMAD4 and cancer: Despite this, measuring blood-derived culturesof both healthy and cancer patients revealed an upregulation of MG-AGEsin those with cancer.251 Furthermore, thepro-cancer role of AGE/RAGE activation and its downstream signalingcascades has been well established across multiple types of cancers,showing it inhibits apoptosis252 and promotesautophagy,252 angiogenesis via VEGF,146 growth,253 inflammation,146 and metastasis via pathways such as AP-1, NFκB,STAT3, SMAD4, MAPK, mTOR, and PI3K.119,254−257