CFLAR and colonic neoplasm: Interestingly, recent data have revealed that TRAILR2/DR5 upregulation and apoptosis in 2D cultures of colon tumor cells undergoing ER stress are preceded by an early decrease in the protein levels of both FLIP isoforms, which alters the caspase-8/FLIP ratio, facilitating caspase-8 activation at the intracellular DISC and the subsequent induction of apoptosis [69], as has been demonstrated in TRAIL-induced apoptosis [64,65].