FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2914971500> ?p ?o ?g. }

• W2914971500 endingPage "1333" @default.
• W2914971500 startingPage "1320" @default.
• W2914971500 abstract "It is increasingly appreciated that 3D cultures are more predictive of in vivo therapeutic efficacy than 2D cultures. Using in vitro 3D type I collagen cultures of human colorectal cancer (CRC) cell line HCA-7 derivatives CC, SC, and CC-CR, we previously identified that activation of receptor tyrosine kinases (RTKs) MET and RON contributed to resistance to the EGF receptor (EGFR)-directed therapeutic antibody cetuximab. The de novo mode of cetuximab resistance in SC cells could be overcome by crizotinib, a multi-RTK inhibitor that also targets MET and RON. We now show that crizotinib also overcomes acquired cetuximab resistance in CC-CR cells. Phospho-RTK array analysis showed increased phosphorylation of several RTKs, including MET and RON, in SC and CC-CR cells compared to cetuximab-sensitive CC counterparts. Furthermore, other multi-RTK inhibitors cabozantinib and BMS-777607 helped overcome cetuximab resistance, as measured by 3D colony growth and activation state of key signaling molecules. Conversely, addition of RTK ligands HGF and NRG1 induced cetuximab resistance in CC cells, which could be blocked by addition of crizotinib. We further determined the mechanism of the cooperative effect of cetuximab and crizotinib by FACS analysis and observed increased cell cycle arrest in G1 phase in cetuximab-resistant CRC 3D cultures. Finally, we show that crizotinib overcomes cetuximab resistance in vivo in SC nude mice xenografts. Thus, our work shows that multi-RTK inhibition strategy is a potent, broadly applicable strategy to overcome resistance to EGFR-targeted therapeutics in CRC and highlights the relevance of 3D cultures in these studies. Statement of implication: Using in vitro 3D CRC cultures and in vivo CRC xenografts, we show that parallel inhibition of multiple RTKs with small molecule inhibitors overcomes de novo and acquired resistance to EGFR-directed therapies in CRC." @default.
• W2914971500 created "2019-02-21" @default.
• W2914971500 creator A5005791249 @default.
• W2914971500 creator A5018831070 @default.
• W2914971500 creator A5026710055 @default.
• W2914971500 creator A5036988988 @default.
• W2914971500 creator A5041399222 @default.
• W2914971500 creator A5090179644 @default.
• W2914971500 date "2019-02-12" @default.
• W2914971500 modified "2023-09-27" @default.
• W2914971500 title "Broad-spectrum receptor tyrosine kinase inhibitors overcome <i>de novo</i> and acquired modes of resistance to EGFR-targeted therapies in colorectal cancer" @default.
• W2914971500 cites W1557061959 @default.
• W2914971500 cites W1875361486 @default.
• W2914971500 cites W1966803171 @default.
• W2914971500 cites W1971001418 @default.
• W2914971500 cites W1984101180 @default.
• W2914971500 cites W1987443121 @default.
• W2914971500 cites W1998971866 @default.
• W2914971500 cites W2006168411 @default.
• W2914971500 cites W2007513598 @default.
• W2914971500 cites W2033478817 @default.
• W2914971500 cites W2041919461 @default.
• W2914971500 cites W2054614254 @default.
• W2914971500 cites W2057623977 @default.
• W2914971500 cites W2058522541 @default.
• W2914971500 cites W2062109911 @default.
• W2914971500 cites W2093613683 @default.
• W2914971500 cites W2096470960 @default.
• W2914971500 cites W2102354469 @default.
• W2914971500 cites W2106789440 @default.
• W2914971500 cites W2113097723 @default.
• W2914971500 cites W2116168356 @default.
• W2914971500 cites W2116407319 @default.
• W2914971500 cites W2116731538 @default.
• W2914971500 cites W2122375037 @default.
• W2914971500 cites W2129172946 @default.
• W2914971500 cites W2133129337 @default.
• W2914971500 cites W2134519717 @default.
• W2914971500 cites W2140035322 @default.
• W2914971500 cites W2142564546 @default.
• W2914971500 cites W2155311724 @default.
• W2914971500 cites W2164837623 @default.
• W2914971500 cites W2168377135 @default.
• W2914971500 cites W2184198667 @default.
• W2914971500 cites W2265437850 @default.
• W2914971500 cites W2559749825 @default.
• W2914971500 cites W2589900383 @default.
• W2914971500 cites W2597422592 @default.
• W2914971500 cites W2598988806 @default.
• W2914971500 cites W2754348276 @default.
• W2914971500 cites W2766837662 @default.
• W2914971500 cites W2795353688 @default.
• W2914971500 cites W2795979587 @default.
• W2914971500 cites W4211173486 @default.
• W2914971500 doi "https://doi.org/10.18632/oncotarget.26663" @default.
• W2914971500 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/6407678" @default.
• W2914971500 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30863492" @default.
• W2914971500 hasPublicationYear "2019" @default.
• W2914971500 type Work @default.
• W2914971500 sameAs 2914971500 @default.
• W2914971500 citedByCount "10" @default.
• W2914971500 countsByYear W29149715002019 @default.
• W2914971500 countsByYear W29149715002020 @default.
• W2914971500 countsByYear W29149715002021 @default.
• W2914971500 countsByYear W29149715002022 @default.
• W2914971500 crossrefType "journal-article" @default.
• W2914971500 hasAuthorship W2914971500A5005791249 @default.
• W2914971500 hasAuthorship W2914971500A5018831070 @default.
• W2914971500 hasAuthorship W2914971500A5026710055 @default.
• W2914971500 hasAuthorship W2914971500A5036988988 @default.
• W2914971500 hasAuthorship W2914971500A5041399222 @default.
• W2914971500 hasAuthorship W2914971500A5090179644 @default.
• W2914971500 hasBestOaLocation W29149715001 @default.
• W2914971500 hasConcept C101544691 @default.
• W2914971500 hasConcept C121608353 @default.
• W2914971500 hasConcept C126322002 @default.
• W2914971500 hasConcept C143998085 @default.
• W2914971500 hasConcept C150903083 @default.
• W2914971500 hasConcept C167734588 @default.
• W2914971500 hasConcept C170493617 @default.
• W2914971500 hasConcept C207001950 @default.
• W2914971500 hasConcept C2776232967 @default.
• W2914971500 hasConcept C2776256026 @default.
• W2914971500 hasConcept C2777506169 @default.
• W2914971500 hasConcept C2779422266 @default.
• W2914971500 hasConcept C2779438470 @default.
• W2914971500 hasConcept C2779998722 @default.
• W2914971500 hasConcept C2781064419 @default.
• W2914971500 hasConcept C42362537 @default.
• W2914971500 hasConcept C502942594 @default.
• W2914971500 hasConcept C526805850 @default.
• W2914971500 hasConcept C71924100 @default.
• W2914971500 hasConcept C86803240 @default.
• W2914971500 hasConceptScore W2914971500C101544691 @default.
• W2914971500 hasConceptScore W2914971500C121608353 @default.
• W2914971500 hasConceptScore W2914971500C126322002 @default.
• W2914971500 hasConceptScore W2914971500C143998085 @default.
• W2914971500 hasConceptScore W2914971500C150903083 @default.

• next