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Peter Ujhazy



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    ES 09 - Recent Progress in the Management of Small Cell Lung Cancer (ID 518)

    • Event: WCLC 2017
    • Type: Educational Session
    • Track: SCLC/Neuroendocrine Tumors
    • Presentations: 1
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      ES 09.06 - NCI’s Small Cell Lung Cancer Consortium: New Answers to Old Questions (ID 10941)

      15:50 - 16:10  |  Presenting Author(s): Peter Ujhazy

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      • Presentation
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      Abstract:
      The worldwide toll in mortality due to small cell lung cancer (SCLC) is still unacceptable. Based on an analysis conducted by the National Cancer Institute US (NCI) in 2014, there are five priorities in SCLC that need to be addressed by scientists and clinicians: 1. Development of better research tools for the study of SCLC; 2. Conduct of comprehensive genomic profiling of SCLC; 3. Creation of new diagnostic and prevention approaches for SCLC; 4. Therapeutic development efforts; and 5. Study of mechanisms underlying both high rate of initial response and rapid emergence of drug and radiation resistance. These priorities are being currently addressed by the newly established NCIs SCLC Consortium, an effort to coordinate and network investigators focusing on pre-clinical studies of the disease. The SCLC Consortium currently includes a coordinating resource center, members with their individual projects, and associate members funded through other grant mechanisms. The Principal Investigator of the Coordinating Center is Dr. Charles Rudin from the Sloan Kettering Institute for Cancer Research in New York, NY and he is joined by Drs. John Minna (University of Texas South Western), Tyler Jacks (Broad Institute), You Shyr (Vanderbilt University), and Afshin Dowlati (Case Western Reserve University). The Coordinating Center provides administrative, meeting, and communication support, a bioinformatics database, centralized tissue banking and virtual biospecimen database, centralized biostatistics, cell line and animal model repository. The four Research Projects in the Consortium were selected by a standard peer review process and they focus on: 1) the use of extracellular vesicles for early detection of SCLC; 2) preclinical development of a DLL3-targeted theranostic for SCLC; 3) targeting the transcriptional and epigenetic landscape in chemo-refractory SCLC; and 4) novel therapeutic approaches for enhancing anti-tumor immunity in SCLC. The first project, led by Drs. Serge Nana-Sinkam from Virginia Commonwealth University and James Lee from Ohio State University attempts to carry out an analysis of nucleic acids found in exosomes using molecular beacons contained on biochips to detect specific mRNA and miRNA sequences. The hypothesis is that unique nucleic acid differences in exosomes exist that can differentiate among normal smokers and SCLC patients. The goal is to obtain a biochip that can be used as a biomarker for early stage SCLC that can be applied broadly to blood samples. The second project is conducted by Dr. John Thomas Poirer (Sloan Kettering Institute for Cancer Research) and it builds on the earlier clinical success of the antibody-drug conjugate against a ligand of the Notch pathway, DLL3, selectively expressed on the surface of SCLC cells. The new project will develop a radioimmunotherapy reagent targeted against DLL3, expressed in 70-80% of SCLC. If even moderately successful, this work may provide therapeutic options to some patients who currently have none. The third project designed by Drs. Kwok Kin Wong from New York University and Nathanael Schiander Gray from Dana-Farber Harvard Cancer Institute aims to define transcriptional and epigenetic factors that contribute to chemotherapy-resistance in both tumor cells and the surrounding microenvironment and assess the efficacy of transcriptional CDK inhibitors alone or in combination with novel investigational therapies, utilizing in vivo SCLC models. This is a compelling, well-rationalized, project that pursues an important new direction for both understanding the fundamental biology of SCLC tumor cells and exploiting that information for therapeutic development. The latest addition to the Consortium is project 4 by John Heymach, Lauren Byers (both from the University of Texas MD Anderson Cancer Center), and Julien Sage from Stanford University. The investigators seek to identify improved treatment strategies in SCLC using immunotherapeutic agents targeting the PD1 pathway. The overarching goals of this project are to exploit the intersection of DNA damage repair and immunotherapy in SCLC for new targets and therapies, and to enhance the benefit of existing therapeutic options or ongoing clinical studies. Besides the main Research Projects, the Consortium serves as a hub for Associate Members with additional SCLC projects funded through NCI grants. The topics of these projects include new determinants of acquired resistance, Notch signaling in SCLC, molecular and cellular mechanisms of metastasis, therapeutic strategies for targeting PARP1, kinase dependent chemotherapy resistance mechanisms, and investigating CREBBP as a tumor suppressor. The NCI accepts applications for membership in the SCLC Consortium through two program announcements PAR-16-049 and PAR-16-051. International teams are encouraged to apply.

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