Combination effects of SMAC mimetic birinapant with TNFα, TRAIL, and docetaxel in preclinical models of HNSCC.

ABSTRACT:

Objectives/hypothesis

Head and neck squamous cell carcinoma (HNSCC) cells are resistant to cell death induced by tumor necrosis factor ligands such as tumor necrosis factor α (TNFα) or TNF-related apoptosis-inducing ligand (TRAIL) and cytotoxic chemotherapies. Recently, genetic alterations in cell death pathways, including inhibitor of apoptosis proteins, have been demonstrated in HNSCC. We investigated the effects of birinapant, a novel, second mitochondria-derived activator of caspases (SMAC)-mimetic that targets inhibitor of apoptosis proteins, alone and in combination with TNFα, TRAIL, or chemotherapy docetaxel.

Study design

Experimental study using human HNSCC cell lines in vitro and xenograft mouse model in vivo.

Methods

A panel of HNSCC cell lines with varying

SUBMITTER: Eytan DF 

PROVIDER: S-EPMC4336212 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature