Combined TRIP13 and Aurora Kinase Inhibition Induces Apoptosis in Human Papillomavirus-Driven Cancers.

ABSTRACT:

Purpose

Human papillomavirus (HPV) causes >5% of cancers, but no therapies uniquely target HPV-driven cancers.

Experimental design

We tested the cytotoxic effect of 864 drugs in 16 HPV-positive and 17 HPV-negative human squamous cancer cell lines. We confirmed apoptosis in vitro and in vivo using patient-derived xenografts. Mitotic pathway components were manipulated with drugs, knockdown, and overexpression.

Results

Aurora kinase inhibitors were more effective in vitro and in vivo in HPV-positive than in HPV-negative models. We hypothesized that the mechanism of sensitivity involves retinoblastoma (Rb) expression because the viral oncoprotein E7 leads to Rb protein degradation, and basal Rb protein expression correlates with Aurora inhibition-induced apoptosis. Manip

SUBMITTER: Ghosh S 

PROVIDER: S-EPMC9588713 | biostudies-literature | 2022 Oct

REPOSITORIES: biostudies-literature