Abstract C5: FLIP protein-protein interaction inhibitors enhance sensitivity of colorectal cancer cells to chemotherapy and TRAIL

Abstract:

Background Colorectal Cancer (CRC) is the second most common cause of cancer death, with 40% of patients with this disease obtaining no benefit from current chemotherapy. Novel therapeutic strategies are needed to improve CRC patient response rates and survival. FLIP is an inhibitor of the extrinsic apoptotic pathway that binds to FADD at death-inducing signalling complexes (DISCs), such as those formed by the TNF-α-related apoptosis inducing ligand (TRAIL) receptors TRAIL-R1 and TRAIL-R2, thereby blocking homodimerization and activation of procaspase-8 and inhibiting apoptosis induction. We previously reported that FLIP blocks apoptosis induced by TRAIL and standard-of-care chemotherapeutics (5-Fluorouracil, oxaliplatin and SN38) in CRC models. Moreover, FLIP is frequently overexpressed in CRC and its overexpression correlates with poor prognosis. Subsequently, we have developed novel …

Año de publicación:

2015

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