04-03-2021 дата публикации
Номер: US20210060006A1
Принадлежит:
The present invention provides, inter alia, methods for treating or ameliorating the effects of a cancer in a subject, e.g., glioblastoma (GBM) in a subject that is resistant to temozolomide (TMZ), methods for delaying the emergence of TMZ resistance and/or increasing the TMZ sensitivity in a subject, and methods for reducing tumor aggressiveness in a subject. Also provided are pharmaceutical compositions and kits to implement such methods. 1. A method for treating or ameliorating the effects of a cancer in a subject , comprising administering to the subject a therapeutically effective amount of a first agent that modulates the activity of an enhancer and a therapeutically effective amount of a second agent that is used to treat the cancer.2. The method of claim 1 , wherein the enhancer regulates the expression of O-methylguanine-DNA-methyltransferase (MGMT) and/or Ki67 in the subject.3. The method of claim 1 , wherein the first agent is selected from a Bromodomain inhibitor (BETi) claim 1 , a histone acetyltransferase inhibitor (HATi) claim 1 , and combinations thereof.4. The method of claim 3 , wherein the Bromodomain inhibitor (BETi) is selected from the group consisting of JQ1 claim 3 , I-BET151/762 claim 3 , PF-1 claim 3 , RVX-208 claim 3 , BMS-986158 claim 3 , OTX015 claim 3 , PLX-51107 claim 3 , GSK525762 claim 3 , INCB054329 claim 3 , TEN-010 claim 3 , GSK2820151 claim 3 , BAY 1238097 claim 3 , and combinations thereof.5. The method of claim 3 , wherein the histone acetyltransferase inhibitor (HATi) is selected from the group consisting of C646 claim 3 , NU-9056 claim 3 , PU141 claim 3 , EML425 claim 3 , L002 claim 3 , MB-3 claim 3 , CPTH2 claim 3 , Plumbagin claim 3 , Embelin claim 3 , EGCG claim 3 , Curcumin claim 3 , HAT inhibitor II claim 3 , Garcinol claim 3 , Anacardic acid claim 3 , MG 149 claim 3 , Gossypol claim 3 , CTK7A claim 3 , Windorphen claim 3 , LoCAM claim 3 , TH1834 claim 3 , CTx-1 claim 3 , Lys-CoA claim 3 , and combinations thereof.6. The ...
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