Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387609462> ?p ?o ?g. }
- W4387609462 abstract "Inherent or acquired resistance to sotorasib poses a substantialt challenge for NSCLC treatment. Here, we demonstrate that acquired resistance to sotorasib in isogenic cells correlated with increased expression of integrin β4 (ITGB4), a component of the focal adhesion complex. Silencing ITGB4 in tolerant cells improved sotorasib sensitivity, while overexpressing ITGB4 enhanced tolerance to sotorasib by supporting AKT-mTOR bypass signaling. Chronic treatment with sotorasib induced WNT expression and activated the WNT/β-catenin signaling pathway. Thus, silencing both ITGB4 and β-catenin significantly improved sotorasib sensitivity in tolerant, acquired, and inherently resistant cells. In addition, the proteasome inhibitor carfilzomib (CFZ) exhibited synergism with sotorasib by down-regulating ITGB4 and β-catenin expression. Furthermore, adagrasib phenocopies the combination effect of sotorasib and CFZ by suppressing KRAS activity and inhibiting cell cycle progression in inherently resistant cells. Overall, our findings unveil previously unrecognized nongenetic mechanisms underlying resistance to sotorasib and propose a promising treatment strategy to overcome resistance." @default.
- W4387609462 created "2023-10-14" @default.
- W4387609462 creator A5000500580 @default.
- W4387609462 creator A5002258345 @default.
- W4387609462 creator A5005554864 @default.
- W4387609462 creator A5006711911 @default.
- W4387609462 creator A5007937560 @default.
- W4387609462 creator A5012380163 @default.
- W4387609462 creator A5013374786 @default.
- W4387609462 creator A5017980532 @default.
- W4387609462 creator A5018001380 @default.
- W4387609462 creator A5020914791 @default.
- W4387609462 creator A5023147671 @default.
- W4387609462 creator A5025544408 @default.
- W4387609462 creator A5027357642 @default.
- W4387609462 creator A5028021994 @default.
- W4387609462 creator A5028397846 @default.
- W4387609462 creator A5028715423 @default.
- W4387609462 creator A5033217311 @default.
- W4387609462 creator A5034151974 @default.
- W4387609462 creator A5034609249 @default.
- W4387609462 creator A5040367016 @default.
- W4387609462 creator A5042452505 @default.
- W4387609462 creator A5051698935 @default.
- W4387609462 creator A5051970161 @default.
- W4387609462 creator A5055165247 @default.
- W4387609462 creator A5059052987 @default.
- W4387609462 creator A5061012285 @default.
- W4387609462 creator A5064296485 @default.
- W4387609462 creator A5064506130 @default.
- W4387609462 creator A5064759824 @default.
- W4387609462 creator A5067213000 @default.
- W4387609462 creator A5078636533 @default.
- W4387609462 creator A5085256777 @default.
- W4387609462 creator A5086281302 @default.
- W4387609462 creator A5087056879 @default.
- W4387609462 creator A5090154787 @default.
- W4387609462 date "2023-10-13" @default.
- W4387609462 modified "2023-10-18" @default.
- W4387609462 title "Acquired resistance to KRAS G12C small-molecule inhibitors via genetic/nongenetic mechanisms in lung cancer" @default.
- W4387609462 cites W1696775091 @default.
- W4387609462 cites W1915767302 @default.
- W4387609462 cites W1948677875 @default.
- W4387609462 cites W1996572869 @default.
- W4387609462 cites W2012302769 @default.
- W4387609462 cites W2023560061 @default.
- W4387609462 cites W2044433401 @default.
- W4387609462 cites W2045509446 @default.
- W4387609462 cites W2060737851 @default.
- W4387609462 cites W2098272135 @default.
- W4387609462 cites W2108234281 @default.
- W4387609462 cites W2111711361 @default.
- W4387609462 cites W2114104545 @default.
- W4387609462 cites W2129590156 @default.
- W4387609462 cites W2130410032 @default.
- W4387609462 cites W2131478115 @default.
- W4387609462 cites W2134526812 @default.
- W4387609462 cites W2137129298 @default.
- W4387609462 cites W2137586531 @default.
- W4387609462 cites W2146486175 @default.
- W4387609462 cites W2149308715 @default.
- W4387609462 cites W2152320398 @default.
- W4387609462 cites W2154431984 @default.
- W4387609462 cites W2168133698 @default.
- W4387609462 cites W2169456326 @default.
- W4387609462 cites W2214074259 @default.
- W4387609462 cites W2276748084 @default.
- W4387609462 cites W2335854816 @default.
- W4387609462 cites W2346906535 @default.
- W4387609462 cites W2474049609 @default.
- W4387609462 cites W2621470440 @default.
- W4387609462 cites W2767162493 @default.
- W4387609462 cites W2781356709 @default.
- W4387609462 cites W2783238692 @default.
- W4387609462 cites W2784371446 @default.
- W4387609462 cites W2785797026 @default.
- W4387609462 cites W2790754944 @default.
- W4387609462 cites W2891963960 @default.
- W4387609462 cites W2904683700 @default.
- W4387609462 cites W2906754611 @default.
- W4387609462 cites W2911653939 @default.
- W4387609462 cites W2953572098 @default.
- W4387609462 cites W2975790812 @default.
- W4387609462 cites W2976596814 @default.
- W4387609462 cites W2981475131 @default.
- W4387609462 cites W2990871782 @default.
- W4387609462 cites W2995793704 @default.
- W4387609462 cites W2998581726 @default.
- W4387609462 cites W2999810289 @default.
- W4387609462 cites W3042846250 @default.
- W4387609462 cites W3080542372 @default.
- W4387609462 cites W3087229737 @default.
- W4387609462 cites W3119145039 @default.
- W4387609462 cites W3129815975 @default.
- W4387609462 cites W3130322169 @default.
- W4387609462 cites W3142010099 @default.
- W4387609462 cites W3157480760 @default.
- W4387609462 cites W3163195272 @default.
- W4387609462 cites W3167360675 @default.
- W4387609462 cites W3171675220 @default.