Publications by authors named "J L Kutok"
Background: Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with a poor prognosis particularly in the metastatic setting. Treatments with anti-programmed cell death protein-1/programmed death-ligand 1 (PD-L1) immune checkpoint inhibitors (ICI) in combination with chemotherapies have demonstrated promising clinical benefit in metastatic TNBC (mTNBC) but there is still an unmet need, particularly for patients with PD-L1 negative tumors. Mechanisms of resistance to ICIs in mTNBC include the presence of immunosuppressive tumor-associated macrophages (TAMs) in the tumor microenvironment (TME).
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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.