Proteomics

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Differential activity of treatment with protein kinase inhibitors on tumor phosphotyrosine profiles in patients with advanced cancer

ABSTRACT: Mass spectrometry-based phosphoproteomics of tumor tissue lysates provides a potential personalized medicine approach based on its ability to identify activated signaling pathways and novel drug targets. We performed a pilot study (NCT01636908) to determine the effect of protein kinase inhibitors (PKIs) on tyrosine-(pTyr)-phosphoproteomic profiles of serial tumor biopsies in patients with advanced cancer. Tumor needle biopsies were analyzed from 31 patients with advanced cancer before and after 2 weeks treatment with sorafenib (SOR), erlotinib (ERL), dasatinib (DAS), vemurafenib (VEM), sunitinib (SUN) or everolimus (EVE). pTyr-Phosphoproteomics of pre- and on-treatment biopsies was performed by phosphotyrosine immunoprecipitation followed by LC-MS/MS.

INSTRUMENT(S): Q Exactive

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Liver, Epithelial Cell, Prostate Cancer Cell, Skin, Colon, Pancreas, Kidney, Esophagus

DISEASE(S): Colon Cancer,Melanoma,Esophageal Cancer,Prostate Cancer,Pancreatic Cancer,Kidney Cancer,Hepatocellular Carcinoma

SUBMITTER: Sander Piersma  

LAB HEAD: Connie Ramona Jimenez

PROVIDER: PXD008032 | Pride | 2019-04-18

REPOSITORIES: Pride

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Identification of predictive biomarkers for targeted therapies requires information on drug exposure at the target site as well as its effect on the signaling context of a tumor. To obtain more insight in the clinical mechanism of action of protein kinase inhibitors (PKIs), we studied tumor drug concentrations of protein kinase inhibitors (PKIs) and their effect on the tyrosine-(pTyr)-phosphoproteome in patients with advanced cancer. Tumor biopsies were obtained from 31 patients with advanced ca  ...[more]

PMID: 32024067

Publication: 1/2

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