First Author | Reyzer ML | Year | 2004 |
Journal | Cancer Res | Volume | 64 |
Issue | 24 | Pages | 9093-100 |
PubMed ID | 15604278 | Mgi Jnum | J:94959 |
Mgi Id | MGI:3522375 | Doi | 10.1158/0008-5472.CAN-04-2231 |
Citation | Reyzer ML, et al. (2004) Early changes in protein expression detected by mass spectrometry predict tumor response to molecular therapeutics. Cancer Res 64(24):9093-100 |
abstractText | Biomarkers that predict therapeutic response are essential for the development of anticancer therapies. We have used matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) to directly analyze protein profiles in mouse mammary tumor virus/HER2 transgenic mouse frozen tumor sections after treatment with the erbB receptor inhibitors OSI-774 and Herceptin. Inhibition of tumor cell proliferation and induction of apoptosis and tumor reduction were predicted by a >80% reduction in thymosin beta4 and ubiquitin levels that were detectable after 16 hours of a single drug dose before any evidence of in situ cellular activity. These effects were time- and dose-dependent, and their spatial distribution in the tumor correlated with that of the small-molecule inhibitor OSI-774. In addition, they predicted for therapeutic synergy of OSI-774 and Herceptin as well as for drug resistance. These results suggest that drug-induced early proteomic changes as measured by MALDI-MS can be used to predict the therapeutic response to established and novel therapies. |