Matches in SemOpenAlex for { <https://semopenalex.org/work/W4283018982> ?p ?o ?g. }
- W4283018982 abstract "The majority of BRCA1-mutant breast cancers are characterized by a triple-negative phenotype and a basal-like molecular subtype, associated with aggressive clinical behavior. Current treatment options are limited, highlighting the need for the development of novel targeted therapies for this tumor subtype.Our group previously showed that EZH2 is functionally relevant in BRCA1-deficient breast tumors and blocking EZH2 enzymatic activity could be a potent treatment strategy. To validate the role of EZH2 as a therapeutic target and to identify new synergistic drug combinations, we performed a high-throughput drug combination screen in various cell lines derived from BRCA1-deficient and -proficient mouse mammary tumors.We identified the combined inhibition of EZH2 and the proximal DNA damage response kinase ATM as a novel synthetic lethality-based therapy for the treatment of BRCA1-deficient breast tumors. We show that the combined treatment with the EZH2 inhibitor GSK126 and the ATM inhibitor AZD1390 led to reduced colony formation, increased genotoxic stress, and apoptosis-mediated cell death in BRCA1-deficient mammary tumor cells in vitro. These findings were corroborated by in vivo experiments showing that simultaneous inhibition of EZH2 and ATM significantly increased anti-tumor activity in mice bearing BRCA1-deficient mammary tumors.Taken together, we identified a synthetic lethal interaction between EZH2 and ATM and propose this synergistic interaction as a novel molecular combination for the treatment of BRCA1-mutant breast cancer." @default.
- W4283018982 created "2022-06-18" @default.
- W4283018982 creator A5003246186 @default.
- W4283018982 creator A5003416585 @default.
- W4283018982 creator A5007350056 @default.
- W4283018982 creator A5012658848 @default.
- W4283018982 creator A5018968205 @default.
- W4283018982 creator A5019152379 @default.
- W4283018982 creator A5020861505 @default.
- W4283018982 creator A5022455730 @default.
- W4283018982 creator A5028710105 @default.
- W4283018982 creator A5030035319 @default.
- W4283018982 creator A5036526777 @default.
- W4283018982 creator A5051308531 @default.
- W4283018982 creator A5053942949 @default.
- W4283018982 creator A5059821367 @default.
- W4283018982 creator A5063220327 @default.
- W4283018982 creator A5063380198 @default.
- W4283018982 creator A5066061361 @default.
- W4283018982 creator A5067564695 @default.
- W4283018982 creator A5079876641 @default.
- W4283018982 creator A5085355842 @default.
- W4283018982 creator A5088037590 @default.
- W4283018982 creator A5090009576 @default.
- W4283018982 date "2022-06-17" @default.
- W4283018982 modified "2023-10-15" @default.
- W4283018982 title "Combined inhibition of EZH2 and ATM is synthetic lethal in BRCA1-deficient breast cancer" @default.
- W4283018982 cites W107239320 @default.
- W4283018982 cites W1523531555 @default.
- W4283018982 cites W1586303233 @default.
- W4283018982 cites W1724512254 @default.
- W4283018982 cites W1965657711 @default.
- W4283018982 cites W1978780879 @default.
- W4283018982 cites W1982172799 @default.
- W4283018982 cites W1987322786 @default.
- W4283018982 cites W2004380688 @default.
- W4283018982 cites W2013149980 @default.
- W4283018982 cites W2014599726 @default.
- W4283018982 cites W2015132841 @default.
- W4283018982 cites W2030246401 @default.
- W4283018982 cites W2041594739 @default.
- W4283018982 cites W2043567949 @default.
- W4283018982 cites W2046083330 @default.
- W4283018982 cites W2048122601 @default.
- W4283018982 cites W2048617427 @default.
- W4283018982 cites W2054646144 @default.
- W4283018982 cites W2060737851 @default.
- W4283018982 cites W2063851753 @default.
- W4283018982 cites W2066969492 @default.
- W4283018982 cites W2072887636 @default.
- W4283018982 cites W2096745115 @default.
- W4283018982 cites W2099869529 @default.
- W4283018982 cites W2131654458 @default.
- W4283018982 cites W2133743991 @default.
- W4283018982 cites W2138207763 @default.
- W4283018982 cites W2138733479 @default.
- W4283018982 cites W2145292441 @default.
- W4283018982 cites W2146573461 @default.
- W4283018982 cites W2148192361 @default.
- W4283018982 cites W2152239989 @default.
- W4283018982 cites W2157840751 @default.
- W4283018982 cites W2169456326 @default.
- W4283018982 cites W2263927213 @default.
- W4283018982 cites W2295085830 @default.
- W4283018982 cites W2320983896 @default.
- W4283018982 cites W2471011913 @default.
- W4283018982 cites W2560531298 @default.
- W4283018982 cites W2621271973 @default.
- W4283018982 cites W2625452721 @default.
- W4283018982 cites W2728023387 @default.
- W4283018982 cites W2734897937 @default.
- W4283018982 cites W2791577086 @default.
- W4283018982 cites W2795058985 @default.
- W4283018982 cites W2801956643 @default.
- W4283018982 cites W2807418950 @default.
- W4283018982 cites W2809134358 @default.
- W4283018982 cites W2811135418 @default.
- W4283018982 cites W2895846919 @default.
- W4283018982 cites W2897430921 @default.
- W4283018982 cites W2902084106 @default.
- W4283018982 cites W2908226200 @default.
- W4283018982 cites W2922551185 @default.
- W4283018982 cites W2922760642 @default.
- W4283018982 cites W2942776126 @default.
- W4283018982 cites W2944687997 @default.
- W4283018982 cites W2967941174 @default.
- W4283018982 cites W2968820602 @default.
- W4283018982 cites W2972783946 @default.
- W4283018982 cites W2979207255 @default.
- W4283018982 cites W2985788270 @default.
- W4283018982 cites W2990079331 @default.
- W4283018982 cites W3001127731 @default.
- W4283018982 cites W3014482292 @default.
- W4283018982 cites W3022403689 @default.
- W4283018982 cites W3028304854 @default.
- W4283018982 cites W3033914532 @default.
- W4283018982 cites W3083013039 @default.
- W4283018982 cites W3111886002 @default.
- W4283018982 doi "https://doi.org/10.1186/s13058-022-01534-y" @default.
- W4283018982 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35715861" @default.