Publications by authors named "R Taylor Durall"
We present the first known case of a patient with -driven NUT carcinoma. A 59-year-old woman presented with poorly differentiated squamous cell lung cancer metastatic to the pleura. Eventually, a positive NUT immunohistochemistry, NUT fluorescence in situ hybridization, and RNA next-generation sequencing with a fusion led to the diagnosis of NUT carcinoma.
View Article and Find Full Text PDFUnlabelled: NUT carcinoma (NC) is an aggressive squamous carcinoma defined by the BRD4-NUT fusion oncoprotein. Routinely effective systemic treatments are unavailable for most NC patients. The lack of an adequate animal model precludes identifying and leveraging cell-extrinsic factors therapeutically in NC.
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- NUT carcinoma is an aggressive cancer driven by the BRD4-NUT fusion oncoprotein, but treatments using BET bromodomain inhibitors (BETi) alone have limited effectiveness.
- The study shows that inhibiting EZH2, a protein that silences tumor suppressor genes, with a drug called tazemetostat, effectively blocks the growth of NUT carcinoma cells.
- Combining EZH2 and BET inhibitors leads to stronger anti-cancer effects, blocking tumor growth and prolonging survival in models, highlighting a new strategy for treating NUT carcinoma based on targeting epigenetic regulation.
Article Synopsis
- - NUT carcinoma (NC) is a fast-growing cancer driven by the BRD4-NUT fusion protein, which promotes growth by activating genes; while BET bromodomain inhibitors are a potential treatment, they work better when combined with other therapies.
- - EZH2, a gene silencing enzyme, is essential for NC growth, and its inhibition using tazemetostat significantly reduces NC cell proliferation and restores tumor suppressor gene expression without affecting certain oncogenes.
- - Combining EZH2 inhibitors with BET inhibitors enhances the effectiveness of treatment, leading to greater tumor suppression and longer survival in animal models, with some mice even showing complete remission.
Gα13, a heterotrimeric G protein α subunit of the G12/13 subfamily, is an oncogenic driver in multiple cancer types. Unlike other G protein subfamilies that contribute to cancer progression via amino acid substitutions that abolish their deactivating, intrinsic GTPase activity, Gα13 rarely harbors such mutations in tumors and instead appears to stimulate aberrant cell growth via overexpression as a wildtype form. It is not known why this effect is exclusive to the G12/13 subfamily, nor has a mechanism been elucidated for overexpressed Gα13 promoting tumor progression.
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