Bio

Professional Education


  • Doctor of Philosophy, University of California Berkeley (2010)

Stanford Advisors


Patents


  • Nadine Jahchan; Joel Dudley; Julien Sage; Atul Butte. "United StatesMETHODS FOR THE TREATMENT OF CANCER", THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIVERSITY

Research & Scholarship

Current Research and Scholarly Interests


Investigating the mechanisms of Small Cell Lung Cancer development, progression, and treatment

Teaching

Graduate and Fellowship Programs


Publications

Journal Articles


  • A Drug Repositioning Approach Identifies Tricyclic Antidepressants as Inhibitors of Small Cell Lung Cancer and Other Neuroendocrine Tumors CANCER DISCOVERY Jahchan, N. S., Dudley, J. T., Mazur, P. K., Flores, N., Yang, D., Palmerton, A., Zmoos, A., Vaka, D., Tran, K. Q., Zhou, M., Krasinska, K., Riess, J. W., Neal, J. W., Khatri, P., Park, K. S., Butte, A. J., Sage, J. 2013; 3 (12): 1364-1377

    Abstract

    Small cell lung cancer (SCLC) is an aggressive neuroendocrine subtype of lung cancer with high mortality. We used a systematic drug repositioning bioinformatics approach querying a large compendium of gene expression profiles to identify candidate U.S. Food and Drug Administration (FDA)-approved drugs to treat SCLC. We found that tricyclic antidepressants and related molecules potently induce apoptosis in both chemonaïve and chemoresistant SCLC cells in culture, in mouse and human SCLC tumors transplanted into immunocompromised mice, and in endogenous tumors from a mouse model for human SCLC. The candidate drugs activate stress pathways and induce cell death in SCLC cells, at least in part by disrupting autocrine survival signals involving neurotransmitters and their G protein-coupled receptors. The candidate drugs inhibit the growth of other neuroendocrine tumors, including pancreatic neuroendocrine tumors and Merkel cell carcinoma. These experiments identify novel targeted strategies that can be rapidly evaluated in patients with neuroendocrine tumors through the repurposing of approved drugs.Our work shows the power of bioinformatics-based drug approaches to rapidly repurpose FDA-approved drugs and identifies a novel class of molecules to treat patients with SCLC, a cancer for which no effective novel systemic treatments have been identified in several decades. In addition, our experiments highlight the importance of novel autocrine mechanisms in promoting the growth of neuroendocrine tumor cells.

    View details for DOI 10.1158/2159-8290.CD-13-0183

    View details for Web of Science ID 000328257500023

    View details for PubMedID 24078773

Stanford Medicine Resources: