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Cancer Discovery
Cancer Discovery
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About the Cover

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Sen and colleagues showed that treatment of human small cell lung cancer (SCLC) cell lines with inhibitors of the DNA damage response (DDR) components CHK1 and PARP resulted in increased expression of PD-L1 Further, inhibition of either CHK1 or PARP in immunocompetent genetically engineered mouse models (GEMM) of SCLC resulted in increased levels of cytosolic DNA, which activates the cGAS–STING innate immune signaling pathway to induce IRF3 activation and subsequently drive IFNβ-mediated increases in PD-L1 expression and T-cell recruitment in SCLC GEMMs Consistent with these findings, treatment with a CHK1 or PARP inhibitor enhanced the efficacy of anti–PD-L1 therapy and resulted in SCLC tumor regression in vivo Together, these findings suggest that combined targeting of DDR proteins and immune checkpoint blockade is a potential therapeutic strategy for patients with SCLC For details, please see the article by Sen and colleagues on page 646.

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Cancer Discovery: 9 (5)
May 2019
Volume 9, Issue 5
  • Table of Contents
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Cancer Discovery
eISSN: 2159-8290
ISSN: 2159-8274

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