WOODS, Andrew D., Noah E. BERLOW, Michael V. ORTIZ, Filemon Dela CRUZ, Armaan SIDDIQUEE, Diego F. COUTINHO, Reshma PUROHIT, Katherine E. TRANBARGER FREIER, Joel E. MICHALEK, Melvin LATHARA, Kevin MATLOCK, Ganapati SRIVIVASA, Brigitte ROYER-POKORA, Renata VESELSKÁ, Andrew L. KUNG a Charles KELLER. Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor. Pediatric Blood & Cancer. Wiley, 2022, roč. 69, č. 2, s. "e29401", 12 s. ISSN 1545-5009. Dostupné z: https://dx.doi.org/10.1002/pbc.29401. |
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@article{1803573, author = {Woods, Andrew D. and Berlow, Noah E. and Ortiz, Michael V. and Cruz, Filemon Dela and Siddiquee, Armaan and Coutinho, Diego F. and Purohit, Reshma and Tranbarger Freier, Katherine E. and Michalek, Joel E. and Lathara, Melvin and Matlock, Kevin and Srivivasa, Ganapati and RoyerandPokora, Brigitte and Veselská, Renata and Kung, Andrew L. and Keller, Charles}, article_number = {2}, doi = {http://dx.doi.org/10.1002/pbc.29401}, keywords = {anaplasia; AZD5153; BRD4; MYCN; Wilms tumor}, language = {eng}, issn = {1545-5009}, journal = {Pediatric Blood & Cancer}, title = {Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor}, url = {https://onlinelibrary.wiley.com/doi/full/10.1002/pbc.29401}, volume = {69}, year = {2022} }
TY - JOUR ID - 1803573 AU - Woods, Andrew D. - Berlow, Noah E. - Ortiz, Michael V. - Cruz, Filemon Dela - Siddiquee, Armaan - Coutinho, Diego F. - Purohit, Reshma - Tranbarger Freier, Katherine E. - Michalek, Joel E. - Lathara, Melvin - Matlock, Kevin - Srivivasa, Ganapati - Royer-Pokora, Brigitte - Veselská, Renata - Kung, Andrew L. - Keller, Charles PY - 2022 TI - Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor JF - Pediatric Blood & Cancer VL - 69 IS - 2 SP - "e29401" EP - "e29401" PB - Wiley SN - 15455009 KW - anaplasia KW - AZD5153 KW - BRD4 KW - MYCN KW - Wilms tumor UR - https://onlinelibrary.wiley.com/doi/full/10.1002/pbc.29401 N2 - Background Wilms tumor is the most common childhood kidney cancer. Two distinct histological subtypes of Wilms tumor have been described: tumors lacking anaplasia (the favorable subtype) and tumors displaying anaplastic features (the unfavorable subtype). Children with favorable disease generally have a very good prognosis, whereas those with anaplasia are oftentimes refractory to standard treatments and suffer poor outcomes, leading to an unmet clinical need. MYCN dysregulation has been associated with a number of pediatric cancers including Wilms tumor. Procedures In this context, we undertook a functional genomics approach to uncover novel therapeutic strategies for those patients with anaplastic Wilms tumor. Genomic analysis and in vitro experimentation demonstrate that cell growth can be reduced by modulating MYCN overexpression via bromodomain 4 (BRD4) inhibition in both anaplastic and nonanaplastic Wilms tumor models. Results We observed a time-dependent reduction of MYCN and MYCC protein levels upon BRD4 inhibition in Wilms tumor cell lines, which led to cell death and proliferation suppression. BRD4 inhibition significantly reduced tumor volumes in Wilms tumor patient-derived xenograft (PDX) mouse models. Conclusions We suggest that AZD5153, a novel dual-BRD4 inhibitor, can reduce MYCN levels in both anaplastic and nonanaplastic Wilms tumor cell lines, reduces tumor volume in Wilms tumor PDXs, and should be further explored for its therapeutic potential. ER -
WOODS, Andrew D., Noah E. BERLOW, Michael V. ORTIZ, Filemon Dela CRUZ, Armaan SIDDIQUEE, Diego F. COUTINHO, Reshma PUROHIT, Katherine E. TRANBARGER FREIER, Joel E. MICHALEK, Melvin LATHARA, Kevin MATLOCK, Ganapati SRIVIVASA, Brigitte ROYER-POKORA, Renata VESELSKÁ, Andrew L. KUNG a Charles KELLER. Bromodomain 4 inhibition leads to MYCN downregulation in Wilms tumor. \textit{Pediatric Blood \&{} Cancer}. Wiley, 2022, roč.~69, č.~2, s.~''e29401'', 12 s. ISSN~1545-5009. Dostupné z: https://dx.doi.org/10.1002/pbc.29401.
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