Dual Antagonist of cIAP/XIAP ASTX660 Sensitizes HPV^- and HPV⁺ Head and Neck Cancers to TNFα, TRAIL, and Radiation Therapy.

ABSTRACT:

Purpose

Human papillomavirus-negative (HPV^-) head and neck squamous cell carcinomas (HNSCC) harbor frequent genomic amplification of Fas-associated death domain, with or without concurrent amplification of Baculovirus inhibitor of apoptosis repeat containing (BIRC2/3) genes encoding cellular inhibitor of apoptosis proteins 1/2 (cIAP1/2). Antagonists targeting cIAP1 have been reported to enhance sensitivity of HPV^-, but not HPV⁺ tumors, to TNF family death ligands (TNF and TRAIL) and radiation.Experimental Design: We tested a novel dual cIAP/XIAP antagonist ASTX660 in HPV⁺ and HPV^- cell lines in combination with death ligands TNFα and TRAIL, and in preclinical xenograft models with radiation, an inducer of death ligands.

SUBMITTER: Xiao R 

PROVIDER: S-EPMC6825532 | biostudies-literature | 2019 Nov

REPOSITORIES: biostudies-literature