CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer.
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ABSTRACT:
SUBMITTER: Zhang H
PROVIDER: S-EPMC7277075 | biostudies-literature | 2020 Jan
REPOSITORIES: biostudies-literature
Publications
CDK7 Inhibition Potentiates Genome Instability Triggering Anti-tumor Immunity in Small Cell Lung Cancer.
Zhang Hua H Christensen Camilla L CL Dries Ruben R Oser Matthew G MG Deng Jiehui J Diskin Brian B Li Fei F Pan Yuanwang Y Zhang Xuzhu X Yin Yandong Y Papadopoulos Eleni E Pyon Val V Thakurdin Cassandra C Kwiatkowski Nicholas N Jani Kandarp K Rabin Alexandra R AR Castro Dayanne M DM Chen Ting T Silver Heather H Huang Qingyuan Q Bulatovic Mirna M Dowling Catríona M CM Sundberg Belen B Leggett Alan A Ranieri Michela M Han Han H Li Shuai S Yang Annan A Labbe Kristen E KE Almonte Christina C Sviderskiy Vladislav O VO Quinn Max M Donaghue Jack J Wang Eric S ES Zhang Tinghu T He Zhixiang Z Velcheti Vamsidhar V Hammerman Peter S PS Freeman Gordon J GJ Bonneau Richard R Kaelin William G WG Sutherland Kate D KD Kersbergen Ariena A Aguirre Andrew J AJ Yuan Guo-Cheng GC Rothenberg Eli E Miller George G Gray Nathanael S NS Wong Kwok-Kin KK
Cancer cell 20191226 1
Cyclin-dependent kinase 7 (CDK7) is a central regulator of the cell cycle and gene transcription. However, little is known about its impact on genomic instability and cancer immunity. Using a selective CDK7 inhibitor, YKL-5-124, we demonstrated that CDK7 inhibition predominately disrupts cell-cycle progression and induces DNA replication stress and genome instability in small cell lung cancer (SCLC) while simultaneously triggering immune-response signaling. These tumor-intrinsic events provoke a ...[more]
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