Kinomic profiling identifies focal adhesion kinase 1 as a therapeutic target in advanced clear cell renal cell carcinoma.

ABSTRACT: The introduction of targeted therapies has caused a paradigm shift in the treatment of metastatic clear cell (cc)-renal cell carcinoma (RCC). We hypothesized that determining differential kinase activity between primary and metastatic tumor sites may identify critical drivers of progression and relevant therapeutic targets in metastatic disease. Kinomic profiling was performed on primary tumor and metastatic tumor deposits utilizing a peptide substrate microarray to detect relative tyrosine phosphorylation activity. Pharmacologic and genetic loss of function experiments were used to assess the biologic significance of the top scoring kinase on in vitro and in vivo tumor phenotypes. Kinomics identified 7 peptides with increased tyrosine phosphorylation in metastases that were significantly

SUBMITTER: Ghosh AP 

PROVIDER: S-EPMC5438725 | biostudies-literature | 2017 Apr

REPOSITORIES: biostudies-literature