CASP8 and FADD-like apoptosis regulator (CFLAR) (CFLAR)

CASP8 and FADD-like apoptosis regulator (CFLAR), commonly known as c-FLIP, is a critical molecular inhibitor of death receptor-mediated apoptosis [1, 4]. It functions by binding to the Fas-associated death domain (FADD) and procaspase-8 or -10, thereby preventing the formation of the death-inducing signaling complex (DISC) and subsequent caspase activation [1, 5]. CFLAR exists in multiple isoforms, most notably c-FLIP_L and c-FLIP_S, which play complex roles in cell survival and death pathways [1]. In many cancers, CFLAR is significantly overexpressed, allowing tumor cells to evade apoptosis and develop resistance to conventional chemotherapies and targeted therapies like TRAIL [4, 5]. Consequently, CFLAR mRNA has emerged as a therapeutic target, with antisense oligonucleotides and siRNA being developed to knockdown its expression and sensitize cancer cells to pro-apoptotic stimuli [3, 4]. Clinical and preclinical efforts focus on reducing c-FLIP levels to restore apoptotic signaling in malignant cells while managing potential toxicities in normal tissues where c-FLIP provides essential survival signals [3, 5].

Other names

c-FLIPFLAME-1CASP8AP1CASHCLARPMRITI-FLICEUsurpin

Antisense oligonucleotide-mediated degradation of mRNA via RNase H activation, preventing the translation of c-FLIP protein isoforms [3, 4].