Combined BRD4 and CDK9 inhibition as a new therapeutic approach in malignant rhabdoid tumors
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Combined BRD4 and CDK9 inhibition as a new therapeutic approach in malignant rhabdoid tumors. / Moreno, Natalia; Holsten, Till; Mertins, Julius; Zoghbi, Annabelle; Johann, Pascal-David; Kool, Marcel; Meisterernst, Michael; Kerl, Kornelius.
In: ONCOTARGET, Vol. 8, No. 49, 10.2017, p. 84986-84995.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research
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TY - JOUR
T1 - Combined BRD4 and CDK9 inhibition as a new therapeutic approach in malignant rhabdoid tumors
AU - Moreno, Natalia
AU - Holsten, Till
AU - Mertins, Julius
AU - Zoghbi, Annabelle
AU - Johann, Pascal-David
AU - Kool, Marcel
AU - Meisterernst, Michael
AU - Kerl, Kornelius
PY - 2017/10
Y1 - 2017/10
N2 - Rhabdoid tumors are caused by the deletion of SMARCB1, whose protein encodes the SMARCB1 subunit of the chromatin remodeling complex SWI/SNF that is involved in global chromatin organization and gene expression control. Simultaneously inhibiting the main players involved in the deregulated transcription machinery is a promising option for preventing exaggerated tumor cell proliferation and survival as it may bypass compensatory mechanisms. In support of this hypothesis, we report efficient impairment of cellular proliferation and strong induction of cell death elicited by inhibition of bromodomain protein BRD4 and transcription kinase CDK9 using small molecular compounds. Combination of both compounds efficiently represses antiapoptotic genes and the oncogene MYC. Our results provide a novel approach for the treatment of RT.
AB - Rhabdoid tumors are caused by the deletion of SMARCB1, whose protein encodes the SMARCB1 subunit of the chromatin remodeling complex SWI/SNF that is involved in global chromatin organization and gene expression control. Simultaneously inhibiting the main players involved in the deregulated transcription machinery is a promising option for preventing exaggerated tumor cell proliferation and survival as it may bypass compensatory mechanisms. In support of this hypothesis, we report efficient impairment of cellular proliferation and strong induction of cell death elicited by inhibition of bromodomain protein BRD4 and transcription kinase CDK9 using small molecular compounds. Combination of both compounds efficiently represses antiapoptotic genes and the oncogene MYC. Our results provide a novel approach for the treatment of RT.
KW - Journal Article
U2 - 10.18632/oncotarget.18583
DO - 10.18632/oncotarget.18583
M3 - SCORING: Journal article
C2 - 28642448
VL - 8
SP - 84986
EP - 84995
JO - ONCOTARGET
JF - ONCOTARGET
SN - 1949-2553
IS - 49
ER -