Project Overview: Cancer therapeutics targeted against the Epidermal Growth Factor Receptor (EGFR) have demonstrated great potential in lung cancer;however, these agents are effective in only a subset of patients. Furthermore, tumors tliat are initially responsive frequently acquire resistance over time. Though it is straightforward to measure molecular (DNA, RNA, protein) and biophysical (mass, density, charge) characteristics of tumors in bulk, recent studies have shown wide cell-tocell variability and the importance of characterizing that variability in estimating patient outcome^^^. We hypothesize that molecular and biophysical characterizations of circulating cells can discriminate cells that are responsive to therapy from those that are resistant. When analyzing cells collected from the circulation, or from other bodily fluids (e.g., pleural effusions, ascites), typically only a small number of cells are available. To asses the cell-to-cell heterogeneity of this limited number of cells, ive propose to develop and to apply quantitative, comprehensive single-cell analysis devices for assessing the DNA genome (e.g., single nucleotide polymorphisms, fusions, deletions), RNA expression, protein abundance (cell surface, intracellular, and secretome abundance), and biophysical properties of single cells for the dual purposes of predicting a patient's likely response to EGFR-targeted therapies and for monitoring a patient's acquisition of resistance to EGFR-targeted therapies (Fig. N3.3.1). We propose two specific aims for the development, testing, and application of our comprehensive analysis platform (Table N3.3.1).

National Institute of Health (NIH)
National Cancer Institute (NCI)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZCA1-GRB-S)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Stanford University
United States
Zip Code
Si, Peng; Sen, Debasish; Dutta, Rebecca et al. (2017) In Vivo Molecular Optical Coherence Tomography of Lymphatic Vessel Endothelial Hyaluronan Receptors. Sci Rep 7:1086
Liba, Orly; Lew, Matthew D; SoRelle, Elliott D et al. (2017) Speckle-modulating optical coherence tomography in living mice and humans. Nat Commun 8:15845
Feng, Yi; Zhu, Shoujun; Antaris, Alexander L et al. (2017) Live imaging of follicle stimulating hormone receptors in gonads and bones using near infrared II fluorophore. Chem Sci 8:3703-3711
Antaris, Alexander L; Chen, Hao; Diao, Shuo et al. (2017) A high quantum yield molecule-protein complex fluorophore for near-infrared II imaging. Nat Commun 8:15269
Willmann, J├╝rgen K; Bonomo, Lorenzo; Carla Testa, Antonia et al. (2017) Ultrasound Molecular Imaging With BR55 in Patients With Breast and Ovarian Lesions: First-in-Human Results. J Clin Oncol 35:2133-2140
Kani, Kian; Garri, Carolina; Tiemann, Katrin et al. (2017) JUN-Mediated Downregulation of EGFR Signaling Is Associated with Resistance to Gefitinib in EGFR-mutant NSCLC Cell Lines. Mol Cancer Ther 16:1645-1657
Mohanty, Suchismita; Chen, Zixin; Li, Kai et al. (2017) A Novel Theranostic Strategy for MMP-14-Expressing Glioblastomas Impacts Survival. Mol Cancer Ther 16:1909-1921
Liba, Orly; SoRelle, Elliott D; Sen, Debasish et al. (2016) Contrast-enhanced optical coherence tomography with picomolar sensitivity for functional in vivo imaging. Sci Rep 6:23337
Winetraub, Yonatan; SoRelle, Elliott D; Liba, Orly et al. (2016) Quantitative contrast-enhanced optical coherence tomography. Appl Phys Lett 108:023702
SoRelle, Elliott D; Liba, Orly; Campbell, Jos L et al. (2016) A hyperspectral method to assay the microphysiological fates of nanomaterials in histological samples. Elife 5:

Showing the most recent 10 out of 132 publications