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N. Jahchan



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    MS 07 - SCLC Biology & Models (ID 25)

    • Event: WCLC 2015
    • Type: Mini Symposium
    • Track: Biology, Pathology, and Molecular Testing
    • Presentations: 1
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      MS07.03 - Pre-Clinical Mouse Models of SCLC to Identify and Validate New Therapeutic Targets (ID 1874)

      14:50 - 15:05  |  Author(s): N. Jahchan

      • Abstract
      • Presentation
      • Slides

      Abstract:
      Small cell lung cancer (SCLC) is a neuroendocrine subtype of lung cancer characterized by a fast growth rate, extensive dissemination, and rapid resistance to chemotherapy. Survival rates are dismal and have not significantly improved in the past few decades. The group of Roman Thomas and Martin Peifer sequenced the genomes of over 100 human SCLC, which demonstrates universal inactivation of p53 and RB and identified inactivating mutations in NOTCH family genes in ~25% of tumors. Accordingly, we found that activation of Notch signaling in a pre-clinical SCLC mouse model dramatically reduces the number of tumors and extends the survival of the mutant mice. In addition to suppressing proliferation, active Notch inhibits neuroendocrine gene expression in SCLC cells. Thus, Notch plays a key tumor suppressive role in SCLC and strategies to re-activate Notch in SCLC tumors may be beneficial to patients (George, Lim, et al., in press). At the histological level, SCLC tumor cells are often viewed as homogeneous. These studies and previous studies (e.g. Calbo et al., Cancer Cell, 2011 – Berns lab) have identified several levels of intra-tumor heterogeneity in SCLC, which may contribute significantly to SCLC aggressive nature and resistance to therapy. We will also discuss the existence and the role of several subpopulations of SCLC tumor cells involved in the long-term propagation of this cancer type, the rapid acquisition of chemoresistance, and metastasis. A better understanding of the molecular underpinnings of these cellular heterogeneity may help identify novel therapeutic targets in SCLC.

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