@inproceedings{2d75dd99815a44d3b47bdd80c4b4ed39,
title = "Functional diagnostics for precision medicine with silicon photonic microring resonator arrays",
abstract = "Emerging cancer therapies target signaling networks that are overexpressed in cancers. We have developed a phosphoprotein detection panel mapped around the PI3K/Akt/mTOR signaling cascade using microring resonator arrays. We used the panel to monitor signaling dynamics in response to treatment with targeted therapeutics on xenograft explants of glioblastoma tumors. Distinct phosphoprotein profiles were observed as a function of mutational status of the xenograft samples, and the extent of pathway inhibition was dependent on treatment times. This panel detection technology offers substantially higher throughput than global pathway monitoring techniques, such as mass spectrometry-based proteomics or next generation sequencing.",
keywords = "Microring resonators, Precision medicine, Protein detection, Silicon photonics",
author = "Wade, {James H.} and Sarkaria, {Jann N.} and Bailey, {Ryan C.}",
note = "Funding Information: Distinct phosphoprotein profiles were observed as a function of mutational status of the xenograft samples, and the extent of pathway inhibition was dependent on treatment times. This detection technology offers substantially higher throughput Figure 2.Full phosphoprotein profile of GBM 6 and GBM 26 than xenograft explants treated with the EGFR inhibitor erlotinib (n global = 3 samples, 4 replicate rings per sample) pathway monitoring techniques, such as mass spectrometry-based proteomics or next generation sequencing, and the platform has potential to provide actionable information to clinicians guiding selection of optimal targeted therapeutics for cancer treatment. CONCLUSION Several approaches have been used for protein and phosphoprotein detection for tumor analysis. The advantages of the platform include real-time monitoring of binding events, integrated fluidic handling for semi-automated sensor operation, and low limits of detection (LODs) extending to 100s of fg/mL for protein detection applications. In comparison to competing approaches, the microring resonator platform offers a reduced assay time of 1-2 h, which is an improvement upon most array-based methods. In addition, the use of a sandwich immunoassay can result in enhanced specificity in comparison to a single antibody-antigen interaction. With this approach, both patient- and treatment-specific phosphoprotein profiles are obtained, which could be a vital advance for precision medicine. ACKNOWLEDGMENTS The funding for this work was provided by the National Institutes Figure 3. Selected phosphoprotein profiling of Health through the National Cancer Institute (CA177462-01) and the of (A) GBM 6 and (B) GBM 26 treated with National Science Foundation through the Graduate Research the dual PI3K/mTOR inhibitor apitolisib Fellowship Program. (GDC0980, n = 3 samples, 4 replicates per REFERENCES: sample) [1] Wade JH, Alsop AT, Vertin NR, Yang H, Johnson MD, Bailey RC. 2015. ACS Cent. Sci. 1(7):374–82 [2] Tian Q, Sangar V, Price ND. 2016. Mol. Cell. Proteomics. 15(2):362–67 [3] Borrebaeck CAK. 2017. Nat. Rev. Cancer. 17(3):199–204 [4] Pierobon M, Wulfkuhle J, Liotta L, Petricoin E. 2015. Oncogene. 34(7):805–14 [5] Tighe PJ, Ryder RR, Todd I, Fairclough LC. 2015. Proteomics Clin. Appl. 9(3-4):406–22 [6] Sonntag J, et al. 2014/3. Translational Proteomics. 2:52–59 [7] Jeong J, et al. 2016. Proc. Natl. Acad. Sci. U. S. A. 113(3):E282–90 [8] Yu X, Schneiderhan-Marra N, Joos TO. 2010. Clin. Chem. 56(3):376–87 [9] Borrebaeck CAK, Wingren C. 2009. J. Proteomics. 72(6):928–35 [10] Sauer G, et al. 2011. J. Cancer Res. Clin. Oncol. 137(8):1175–84 [11] Nolen BM, et al. 2014. PLoS One. 9(4):e94928 [12] Sarkaria JN, et al. 2007. Mol. Cancer Ther. 6(3):1167–74 [13] Johnson H, el al. 2012. Mol. Cell. Proteomics. 11(12):1724–40 CONTACT * J.H.W. jhwade@umich.edu; R.C.B. ryancb@umich.edu Funding Information: The funding for this work was provided by the National Institutes of Health through the National Cancer Institute (CA177462-01) and the National Science Foundation through the Graduate Research Fellowship Program.; 21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017 ; Conference date: 22-10-2017 Through 26-10-2017",
year = "2020",
language = "English (US)",
series = "21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017",
publisher = "Chemical and Biological Microsystems Society",
pages = "1289--1290",
booktitle = "21st International Conference on Miniaturized Systems for Chemistry and Life Sciences, MicroTAS 2017",
}