Matches in SemOpenAlex for { <https://semopenalex.org/work/W3093371611> ?p ?o ?g. }
- W3093371611 endingPage "136" @default.
- W3093371611 startingPage "123" @default.
- W3093371611 abstract "Cancer chemotherapeutic drugs exert cytotoxic effects by modulating intracellular reactive oxygen species (ROS) levels. However, whether ROS modulates the efficacy of targeted therapeutics remains poorly understood. Previously, we reported that upregulation of the anti-apoptotic protein, BCL-XL, by KRAS activating mutations was a potential target for KRAS-mutant colorectal cancer (CRC) treatment. Here, we demonstrated that the BCL-XL targeting agent, ABT-263, increased intracellular ROS levels and targeting antioxidant pathways augmented the therapeutic efficacy of this BH3 mimetic. ABT-263 induced expression of genes associated with ROS response and increased intracellular ROS levels by enhancing mitochondrial superoxide generation. The superoxide dismutase inhibitor, 2-methoxyestradiol (2-ME), exhibited synergism with ABT-263 in KRAS-mutant CRC cell lines. This synergistic effect was attributed to the inhibition of mTOR-dependent translation of the anti-apoptotic MCL-1 protein via caspase 3-mediated cleavage of AKT and S6K. In addition, combination treatment of ABT-263 and 2-ME demonstrated a synergistic effect in in vivo patient-derived xenografts harboring KRAS mutations. Our data suggest a novel role for ROS in BH3 mimetic-based targeted therapy and provide a novel strategy for treatment of CRC patients with KRAS mutations." @default.
- W3093371611 created "2020-10-22" @default.
- W3093371611 creator A5001434719 @default.
- W3093371611 creator A5003846614 @default.
- W3093371611 creator A5008558105 @default.
- W3093371611 creator A5013714341 @default.
- W3093371611 creator A5032091474 @default.
- W3093371611 creator A5035133412 @default.
- W3093371611 creator A5043442167 @default.
- W3093371611 creator A5051012052 @default.
- W3093371611 creator A5057167506 @default.
- W3093371611 creator A5071440493 @default.
- W3093371611 creator A5078763719 @default.
- W3093371611 creator A5089864521 @default.
- W3093371611 creator A5091554389 @default.
- W3093371611 date "2021-01-01" @default.
- W3093371611 modified "2023-10-10" @default.
- W3093371611 title "Targeting antioxidant enzymes enhances the therapeutic efficacy of the BCL-XL inhibitor ABT-263 in KRAS-mutant colorectal cancers" @default.
- W3093371611 cites W1515607020 @default.
- W3093371611 cites W1552266425 @default.
- W3093371611 cites W1898418248 @default.
- W3093371611 cites W1965987801 @default.
- W3093371611 cites W1967864075 @default.
- W3093371611 cites W1983697833 @default.
- W3093371611 cites W1990350445 @default.
- W3093371611 cites W1991214201 @default.
- W3093371611 cites W1991380853 @default.
- W3093371611 cites W2009333774 @default.
- W3093371611 cites W2009479459 @default.
- W3093371611 cites W2009930854 @default.
- W3093371611 cites W2010984616 @default.
- W3093371611 cites W2019594344 @default.
- W3093371611 cites W2024841712 @default.
- W3093371611 cites W2027395744 @default.
- W3093371611 cites W2031111316 @default.
- W3093371611 cites W2036867510 @default.
- W3093371611 cites W2038683465 @default.
- W3093371611 cites W2047817078 @default.
- W3093371611 cites W2056570604 @default.
- W3093371611 cites W2067091449 @default.
- W3093371611 cites W2068962767 @default.
- W3093371611 cites W2069443403 @default.
- W3093371611 cites W2070202276 @default.
- W3093371611 cites W2077168519 @default.
- W3093371611 cites W2085128107 @default.
- W3093371611 cites W2088370046 @default.
- W3093371611 cites W2103562758 @default.
- W3093371611 cites W2105643937 @default.
- W3093371611 cites W2106930503 @default.
- W3093371611 cites W2114104545 @default.
- W3093371611 cites W2117692326 @default.
- W3093371611 cites W2119316461 @default.
- W3093371611 cites W2123106337 @default.
- W3093371611 cites W2126709547 @default.
- W3093371611 cites W2130410032 @default.
- W3093371611 cites W2134526812 @default.
- W3093371611 cites W2136532871 @default.
- W3093371611 cites W2140318778 @default.
- W3093371611 cites W2160201665 @default.
- W3093371611 cites W2164837623 @default.
- W3093371611 cites W2168632005 @default.
- W3093371611 cites W2169008732 @default.
- W3093371611 cites W2169589032 @default.
- W3093371611 cites W2262414037 @default.
- W3093371611 cites W2277993502 @default.
- W3093371611 cites W2339652075 @default.
- W3093371611 cites W2592029987 @default.
- W3093371611 cites W2620449054 @default.
- W3093371611 cites W2625289674 @default.
- W3093371611 cites W2626044396 @default.
- W3093371611 cites W2769631482 @default.
- W3093371611 cites W2790757017 @default.
- W3093371611 cites W2889646458 @default.
- W3093371611 cites W2924210741 @default.
- W3093371611 cites W2956129706 @default.
- W3093371611 doi "https://doi.org/10.1016/j.canlet.2020.10.018" @default.
- W3093371611 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/33068701" @default.
- W3093371611 hasPublicationYear "2021" @default.
- W3093371611 type Work @default.
- W3093371611 sameAs 3093371611 @default.
- W3093371611 citedByCount "8" @default.
- W3093371611 countsByYear W30933716112021 @default.
- W3093371611 countsByYear W30933716112022 @default.
- W3093371611 countsByYear W30933716112023 @default.
- W3093371611 crossrefType "journal-article" @default.
- W3093371611 hasAuthorship W3093371611A5001434719 @default.
- W3093371611 hasAuthorship W3093371611A5003846614 @default.
- W3093371611 hasAuthorship W3093371611A5008558105 @default.
- W3093371611 hasAuthorship W3093371611A5013714341 @default.
- W3093371611 hasAuthorship W3093371611A5032091474 @default.
- W3093371611 hasAuthorship W3093371611A5035133412 @default.
- W3093371611 hasAuthorship W3093371611A5043442167 @default.
- W3093371611 hasAuthorship W3093371611A5051012052 @default.
- W3093371611 hasAuthorship W3093371611A5057167506 @default.
- W3093371611 hasAuthorship W3093371611A5071440493 @default.
- W3093371611 hasAuthorship W3093371611A5078763719 @default.
- W3093371611 hasAuthorship W3093371611A5089864521 @default.
- W3093371611 hasAuthorship W3093371611A5091554389 @default.