Functional kinomics identifies candidate therapeutic targets in head and neck cancer.

ABSTRACT:

Purpose

To identify novel therapeutic drug targets for p53-mutant head and neck squamous cell carcinoma (HNSCC).

Experimental design

RNAi kinome viability screens were performed on HNSCC cells, including autologous pairs from primary tumor and recurrent/metastatic lesions, and in parallel on murine squamous cell carcinoma (MSCC) cells derived from tumors of inbred mice bearing germline mutations in Trp53, and p53 regulatory genes: Atm, Prkdc, and p19(Arf). Cross-species analysis of cell lines stratified by p53 mutational status and metastatic phenotype was used to select 38 kinase targets. Both primary and secondary RNAi validation assays were performed on additional HNSCC cell lines to credential these kinase targets using multiple phenotypic endpoints. Kinase targets were

SUBMITTER: Moser R 

PROVIDER: S-EPMC4135446 | biostudies-literature | 2014 Aug

REPOSITORIES: biostudies-literature