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Quantitative proteomic profiling identifies protein correlates to EGFR kinase inhibition.

ABSTRACT: Clinical oncology is hampered by lack of tools to accurately assess a patient's response to pathway-targeted therapies. Serum and tumor cell surface proteins whose abundance, or change in abundance in response to therapy, differentiates patients responding to a therapy from patients not responding to a therapy could be usefully incorporated into tools for monitoring response. Here, we posit and then verify that proteomic discovery in in vitro tissue culture models can identify proteins with concordant in vivo behavior and further, can be a valuable approach for identifying tumor-derived serum proteins. In this study, we use stable isotope labeling of amino acids in culture (SILAC) with proteomic technologies to quantitatively analyze the gefitinib-related protein changes in a model system for sensitivity to EGF receptor (EGFR)-targeted tyrosine kinase inhibitors. We identified 3,707 intracellular proteins, 1,276 cell surface proteins, and 879 shed proteins. More than 75% of the proteins identified had quantitative information, and a subset consisting of 400 proteins showed a statistically significant change in abundance following gefitinib treatment. We validated the change in expression profile in vitro and screened our panel of response markers in an in vivo isogenic resistant model and showed that these were markers of gefitinib response and not simply markers of phospho-EGFR downregulation. In doing so, we also were able to identify which proteins might be useful as markers for monitoring response and which proteins might be useful as markers for a priori prediction of response.

SUBMITTER: Kani K

PROVIDER: S-EPMC3959865 | biostudies-literature | 2012 May

REPOSITORIES: biostudies-literature

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Quantitative proteomic profiling identifies protein correlates to EGFR kinase inhibition.

Kani Kian K Faca Vitor M VM Hughes Lindsey D LD Zhang Wenxuan W Fang Qiaojun Q Shahbaba Babak B Luethy Roland R Erde Jonathan J Schmidt Joanna J Pitteri Sharon J SJ Zhang Qing Q Katz Jonathan E JE Gross Mitchell E ME Plevritis Sylvia K SK McIntosh Martin W MW Jain Anjali A Hanash Samir S Agus David B DB Mallick Parag P

Molecular cancer therapeutics 20120312 5

Clinical oncology is hampered by lack of tools to accurately assess a patient's response to pathway-targeted therapies. Serum and tumor cell surface proteins whose abundance, or change in abundance in response to therapy, differentiates patients responding to a therapy from patients not responding to a therapy could be usefully incorporated into tools for monitoring response. Here, we posit and then verify that proteomic discovery in in vitro tissue culture models can identify proteins with conc ...[more]

PMID: 22411897

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Quantitative proteomic profiling identifies protein correlates to EGFR kinase inhibition.

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Quantitative proteomic profiling identifies protein correlates to EGFR kinase inhibition.

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