FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W3024740892> ?p ?o ?g. }

• W3024740892 abstract "Non-small cell lung cancer (NSCLC) patients with activating EGFR mutations initially respond to first-generation EGFR inhibitors; however, the efficacy of these drugs is limited by acquired resistance driven by the EGFR T790M mutation. The discovery of third-generation EGFR inhibitors overcoming EGFR T790M and their new resistance mechanisms have attracted much attention.We examined the antitumor activities and potential resistance mechanism of a novel EGFR third-generation inhibitor in vitro and in vivo using ELISA, SRB assay, immunoblotting, flow cytometric analysis, kinase array, qRT-PCR and tumor xenograft models. The clinical effect on a patient was evaluated by computed tomography scan.We identified compound ASK120067 as a novel inhibitor of EGFR T790M, with selectivity over EGFR WT. ASK120067 exhibited potent anti-proliferation activity in tumor cells harboring EGFR T790M (NCI-H1975) and sensitizing mutations (PC-9 and HCC827) while showed moderate or weak inhibition in cells expressing EGFR WT. Oral administration of ASK120067 induced tumor regression in NSCLC xenograft models and in a PDX model harboring EGFR T790M. The treatment of one patient with advanced EGFR T790M-positive NSCLC was described as proof of principle. Moreover, we found that hyperphosphorylation of Ack1 and the subsequent activation of antiapoptotic signaling via the AKT pathway contributed to ASK120067 resistance. Concomitant targeting of EGFR and Ack1 effectively overrode the acquired resistance of ASK120067 both in vitro and in vivo.Our results idenfity ASK120067 as a promising third-generation EGFR inhibitor and reveal for the first time that Ack1 activation as a novel resistance mechanism to EGFR inhibitors that guide to potential combination strategy." @default.
• W3024740892 created "2020-05-21" @default.
• W3024740892 creator A5001466305 @default.
• W3024740892 creator A5010212263 @default.
• W3024740892 creator A5011166336 @default.
• W3024740892 creator A5035548891 @default.
• W3024740892 creator A5035944487 @default.
• W3024740892 creator A5038805449 @default.
• W3024740892 creator A5041108474 @default.
• W3024740892 creator A5042533031 @default.
• W3024740892 creator A5044598723 @default.
• W3024740892 creator A5045238194 @default.
• W3024740892 creator A5051197797 @default.
• W3024740892 creator A5060848619 @default.
• W3024740892 creator A5061074781 @default.
• W3024740892 creator A5061329349 @default.
• W3024740892 creator A5063800558 @default.
• W3024740892 creator A5069626783 @default.
• W3024740892 creator A5076615377 @default.
• W3024740892 creator A5080277040 @default.
• W3024740892 creator A5081532304 @default.
• W3024740892 creator A5084393924 @default.
• W3024740892 creator A5089348951 @default.
• W3024740892 date "2020-05-13" @default.
• W3024740892 modified "2023-10-14" @default.
• W3024740892 title "Discovery of a novel third-generation EGFR inhibitor and identification of a potential combination strategy to overcome resistance" @default.
• W3024740892 cites W1526983978 @default.
• W3024740892 cites W1546552389 @default.
• W3024740892 cites W1989734503 @default.
• W3024740892 cites W1992398310 @default.
• W3024740892 cites W2002937040 @default.
• W3024740892 cites W2013750047 @default.
• W3024740892 cites W2045555205 @default.
• W3024740892 cites W2055013229 @default.
• W3024740892 cites W2060043463 @default.
• W3024740892 cites W2065293650 @default.
• W3024740892 cites W2074871758 @default.
• W3024740892 cites W2076178766 @default.
• W3024740892 cites W2076785980 @default.
• W3024740892 cites W2081511916 @default.
• W3024740892 cites W2088540000 @default.
• W3024740892 cites W2090029719 @default.
• W3024740892 cites W2095618958 @default.
• W3024740892 cites W2097312459 @default.
• W3024740892 cites W2102088611 @default.
• W3024740892 cites W2146418087 @default.
• W3024740892 cites W2149055519 @default.
• W3024740892 cites W2152636515 @default.
• W3024740892 cites W2154345947 @default.
• W3024740892 cites W2256191967 @default.
• W3024740892 cites W2416111151 @default.
• W3024740892 cites W2465575913 @default.
• W3024740892 cites W2504472048 @default.
• W3024740892 cites W2529451992 @default.
• W3024740892 cites W2559746652 @default.
• W3024740892 cites W2578673768 @default.
• W3024740892 cites W2605449696 @default.
• W3024740892 cites W2605556058 @default.
• W3024740892 cites W2626401975 @default.
• W3024740892 cites W2747965175 @default.
• W3024740892 cites W2765831845 @default.
• W3024740892 cites W2767109827 @default.
• W3024740892 cites W2789780705 @default.
• W3024740892 cites W2792692302 @default.
• W3024740892 cites W2795832970 @default.
• W3024740892 cites W2809739285 @default.
• W3024740892 cites W2889646458 @default.
• W3024740892 cites W2902378590 @default.
• W3024740892 cites W2903482549 @default.
• W3024740892 cites W2903797184 @default.
• W3024740892 cites W2911596654 @default.
• W3024740892 cites W2944167983 @default.
• W3024740892 doi "https://doi.org/10.1186/s12943-020-01202-9" @default.
• W3024740892 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/8369743" @default.
• W3024740892 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/34404402" @default.
• W3024740892 hasPublicationYear "2020" @default.
• W3024740892 type Work @default.
• W3024740892 sameAs 3024740892 @default.
• W3024740892 citedByCount "38" @default.
• W3024740892 countsByYear W30247408922020 @default.
• W3024740892 countsByYear W30247408922021 @default.
• W3024740892 countsByYear W30247408922022 @default.
• W3024740892 countsByYear W30247408922023 @default.
• W3024740892 crossrefType "journal-article" @default.
• W3024740892 hasAuthorship W3024740892A5001466305 @default.
• W3024740892 hasAuthorship W3024740892A5010212263 @default.
• W3024740892 hasAuthorship W3024740892A5011166336 @default.
• W3024740892 hasAuthorship W3024740892A5035548891 @default.
• W3024740892 hasAuthorship W3024740892A5035944487 @default.
• W3024740892 hasAuthorship W3024740892A5038805449 @default.
• W3024740892 hasAuthorship W3024740892A5041108474 @default.
• W3024740892 hasAuthorship W3024740892A5042533031 @default.
• W3024740892 hasAuthorship W3024740892A5044598723 @default.
• W3024740892 hasAuthorship W3024740892A5045238194 @default.
• W3024740892 hasAuthorship W3024740892A5051197797 @default.
• W3024740892 hasAuthorship W3024740892A5060848619 @default.
• W3024740892 hasAuthorship W3024740892A5061074781 @default.
• W3024740892 hasAuthorship W3024740892A5061329349 @default.
• W3024740892 hasAuthorship W3024740892A5063800558 @default.
• W3024740892 hasAuthorship W3024740892A5069626783 @default.

• next