Reference Detail

Ref Type Journal Article
PMID (19584230)
Authors Versele M, Talloen W, Rockx C, Geerts T, Janssen B, Lavrijssen T, King P, Gohlmann HW, Page M, Perera T
Title Response prediction to a multitargeted kinase inhibitor in cancer cell lines and xenograft tumors using high-content tyrosine peptide arrays with a kinetic readout.
Journal Molecular cancer therapeutics
Vol 8
Issue 7
Date 2009 Jul
URL
Abstract Text Multitargeted kinase inhibitors have shown clinical efficacy in a range of cancer types. However, two major problems associated with these drugs are the low fraction of patients for which these treatments provide initial clinical benefit and the occurrence of resistance during prolonged therapy. Several types of predictive biomarkers have been suggested, such as expression level and phosphorylation status of the major targeted kinase(s), mutational status of the kinases involved and of key components of the downstream signaling cascades, and gene expression signatures. In this work, we describe the development of a response prediction platform that does not require prior knowledge of the relevant kinases targeted by the inhibitor; instead, a phosphotyrosine peptide profile using peptide arrays with a kinetic readout is derived in lysates in the presence and absence of a kinase inhibitor. We show in a range of cell lines and in xenograft tumors that this approach allows for the stratification of responders and nonresponders to a multitargeted kinase inhibitor.

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Molecular Profile Treatment Approach
Gene Name Source Synonyms Protein Domains Gene Description Gene Role
Therapy Name Drugs Efficacy Evidence Clinical Trials
Drug Name Trade Name Synonyms Drug Classes Drug Description
Variant Impact Protein Effect Variant Description Associated with drug Resistance
Molecular Profile Indication/Tumor Type Response Type Therapy Name Approval Status Evidence Type Efficacy Evidence References
Unknown unknown stomach cancer not applicable JNJ-26483327 Preclinical Actionable In a preclinical study, human gastric cancer cells demonstrated sensitivity to JNJ-26483327 (PMID: 19584230). 19584230