FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2115647596> ?p ?o ?g. }

• W2115647596 endingPage "2643" @default.
• W2115647596 startingPage "2633" @default.
• W2115647596 abstract "Abstract Mutant KRAS is a feature of more than 25% of non–small cell lung cancers (NSCLC) and represents one of the most prevalent oncogenic drivers in this disease. NSCLC tumors with oncogenic KRAS respond poorly to current therapies, necessitating the pursuit of new treatment strategies. Targeted inhibition of the molecular chaperone Hsp90 results in the coordinated blockade of multiple oncogenic signaling pathways in tumor cells and has thus emerged as an attractive avenue for therapeutic intervention in human malignancies. Here, we examined the activity of ganetespib, a small-molecule inhibitor of Hsp90 currently in clinical trials for NSCLCs in a panel of lung cancer cell lines harboring a diverse spectrum of KRAS mutations. In vitro, ganetespib was potently cytotoxic in all lines, with concomitant destabilization of KRAS signaling effectors. Combinations of low-dose ganetespib with MEK or PI3K/mTOR inhibitors resulted in superior cytotoxic activity than single agents alone in a subset of mutant KRAS cells, and the antitumor efficacy of ganetespib was potentiated by cotreatment with the PI3K/mTOR inhibitor BEZ235 in A549 xenografts in vivo. At the molecular level, ganetespib suppressed activating feedback signaling loops that occurred in response to MEK and PI3K/mTOR inhibition, although this activity was not the sole determinant of combinatorial benefit. In addition, ganetespib sensitized mutant KRAS NSCLC cells to standard-of-care chemotherapeutics of the antimitotic, topoisomerase inhibitor, and alkylating agent classes. Taken together, these data underscore the promise of ganetespib as a single-agent or combination treatment in KRAS-driven lung tumors. Mol Cancer Ther; 11(12); 2633–43. ©2012 AACR." @default.
• W2115647596 created "2016-06-24" @default.
• W2115647596 creator A5010109047 @default.
• W2115647596 creator A5016382860 @default.
• W2115647596 creator A5038282112 @default.
• W2115647596 creator A5056912217 @default.
• W2115647596 creator A5057196078 @default.
• W2115647596 creator A5057787401 @default.
• W2115647596 creator A5079778615 @default.
• W2115647596 creator A5086050220 @default.
• W2115647596 creator A5088356631 @default.
• W2115647596 date "2012-12-01" @default.
• W2115647596 modified "2023-10-12" @default.
• W2115647596 title "Targeting KRAS-Mutant Non–Small Cell Lung Cancer with the Hsp90 Inhibitor Ganetespib" @default.
• W2115647596 cites W1498900438 @default.
• W2115647596 cites W1534608409 @default.
• W2115647596 cites W1970527559 @default.
• W2115647596 cites W1973554661 @default.
• W2115647596 cites W1988533633 @default.
• W2115647596 cites W1991196199 @default.
• W2115647596 cites W1995216176 @default.
• W2115647596 cites W2001999652 @default.
• W2115647596 cites W2006564825 @default.
• W2115647596 cites W2007106751 @default.
• W2115647596 cites W2007340510 @default.
• W2115647596 cites W2009364489 @default.
• W2115647596 cites W2022531767 @default.
• W2115647596 cites W2027052672 @default.
• W2115647596 cites W2029446677 @default.
• W2115647596 cites W2037139573 @default.
• W2115647596 cites W2038947121 @default.
• W2115647596 cites W2039691472 @default.
• W2115647596 cites W2041181609 @default.
• W2115647596 cites W2046993936 @default.
• W2115647596 cites W2050719773 @default.
• W2115647596 cites W2060902443 @default.
• W2115647596 cites W2062272737 @default.
• W2115647596 cites W2081184765 @default.
• W2115647596 cites W2088942787 @default.
• W2115647596 cites W2094595413 @default.
• W2115647596 cites W2099516272 @default.
• W2115647596 cites W2105820269 @default.
• W2115647596 cites W2107318020 @default.
• W2115647596 cites W2114032749 @default.
• W2115647596 cites W2114621192 @default.
• W2115647596 cites W2117479168 @default.
• W2115647596 cites W2121389354 @default.
• W2115647596 cites W2122472408 @default.
• W2115647596 cites W2126427337 @default.
• W2115647596 cites W2126945850 @default.
• W2115647596 cites W2126983941 @default.
• W2115647596 cites W2131303800 @default.
• W2115647596 cites W2131384028 @default.
• W2115647596 cites W2133177414 @default.
• W2115647596 cites W2134370756 @default.
• W2115647596 cites W2137132470 @default.
• W2115647596 cites W2144066782 @default.
• W2115647596 cites W2144370915 @default.
• W2115647596 cites W2144708319 @default.
• W2115647596 cites W2156052827 @default.
• W2115647596 doi "https://doi.org/10.1158/1535-7163.mct-12-0615" @default.
• W2115647596 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/23012248" @default.
• W2115647596 hasPublicationYear "2012" @default.
• W2115647596 type Work @default.
• W2115647596 sameAs 2115647596 @default.
• W2115647596 citedByCount "91" @default.
• W2115647596 countsByYear W21156475962013 @default.
• W2115647596 countsByYear W21156475962014 @default.
• W2115647596 countsByYear W21156475962015 @default.
• W2115647596 countsByYear W21156475962016 @default.
• W2115647596 countsByYear W21156475962017 @default.
• W2115647596 countsByYear W21156475962018 @default.
• W2115647596 countsByYear W21156475962019 @default.
• W2115647596 countsByYear W21156475962020 @default.
• W2115647596 countsByYear W21156475962021 @default.
• W2115647596 countsByYear W21156475962022 @default.
• W2115647596 countsByYear W21156475962023 @default.
• W2115647596 crossrefType "journal-article" @default.
• W2115647596 hasAuthorship W2115647596A5010109047 @default.
• W2115647596 hasAuthorship W2115647596A5016382860 @default.
• W2115647596 hasAuthorship W2115647596A5038282112 @default.
• W2115647596 hasAuthorship W2115647596A5056912217 @default.
• W2115647596 hasAuthorship W2115647596A5057196078 @default.
• W2115647596 hasAuthorship W2115647596A5057787401 @default.
• W2115647596 hasAuthorship W2115647596A5079778615 @default.
• W2115647596 hasAuthorship W2115647596A5086050220 @default.
• W2115647596 hasAuthorship W2115647596A5088356631 @default.
• W2115647596 hasBestOaLocation W21156475961 @default.
• W2115647596 hasConcept C104317684 @default.
• W2115647596 hasConcept C121608353 @default.
• W2115647596 hasConcept C126322002 @default.
• W2115647596 hasConcept C142724271 @default.
• W2115647596 hasConcept C205260736 @default.
• W2115647596 hasConcept C2775932338 @default.
• W2115647596 hasConcept C2776256026 @default.
• W2115647596 hasConcept C2777560012 @default.
• W2115647596 hasConcept C2781187634 @default.
• W2115647596 hasConcept C502942594 @default.

• next