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- W2017187984 abstract "A detailed understanding of the mechanisms by which tumors acquire resistance to targeted anticancer agents should speed the development of treatment strategies with lasting clinical efficacy. RAF inhibition in BRAF-mutant melanoma exemplifies the promise and challenge of many targeted drugs; although response rates are high, resistance invariably develops. Here, we articulate overarching principles of resistance to kinase inhibitors, as well as a translational approach to characterize resistance in the clinical setting through tumor mutation profiling. As a proof of principle, we performed targeted, massively parallel sequencing of 138 cancer genes in a tumor obtained from a patient with melanoma who developed resistance to PLX4032 after an initial dramatic response. The resulting profile identified an activating mutation at codon 121 in the downstream kinase MEK1 that was absent in the corresponding pretreatment tumor. The MEK1 C121S mutation was shown to increase kinase activity and confer robust resistance to both RAF and MEK inhibition in vitro. Thus, MEK1 C121S or functionally similar mutations are predicted to confer resistance to combined MEK/RAF inhibition. These results provide an instructive framework for assessing mechanisms of acquired resistance to kinase inhibition and illustrate the use of emerging technologies in a manner that may accelerate personalized cancer medicine." @default.
- W2017187984 created "2016-06-24" @default.
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- W2017187984 date "2011-08-01" @default.
- W2017187984 modified "2023-10-14" @default.
- W2017187984 title "Dissecting Therapeutic Resistance to RAF Inhibition in Melanoma by Tumor Genomic Profiling" @default.
- W2017187984 cites W1957104301 @default.
- W2017187984 cites W1965871143 @default.
- W2017187984 cites W1968071128 @default.
- W2017187984 cites W1969075054 @default.
- W2017187984 cites W1969228079 @default.
- W2017187984 cites W1971267920 @default.
- W2017187984 cites W1979107490 @default.
- W2017187984 cites W1983852790 @default.
- W2017187984 cites W1985264867 @default.
- W2017187984 cites W1988464631 @default.
- W2017187984 cites W1990376228 @default.
- W2017187984 cites W1992121712 @default.
- W2017187984 cites W1993134078 @default.
- W2017187984 cites W1997476230 @default.
- W2017187984 cites W1998280666 @default.
- W2017187984 cites W1998971866 @default.
- W2017187984 cites W1999614615 @default.
- W2017187984 cites W1999868376 @default.
- W2017187984 cites W1999908952 @default.
- W2017187984 cites W2001447115 @default.
- W2017187984 cites W2001999652 @default.
- W2017187984 cites W2002937040 @default.
- W2017187984 cites W2003984225 @default.
- W2017187984 cites W2005658600 @default.
- W2017187984 cites W2009642188 @default.
- W2017187984 cites W2015015957 @default.
- W2017187984 cites W2015616444 @default.
- W2017187984 cites W2018169163 @default.
- W2017187984 cites W2018789635 @default.
- W2017187984 cites W2026389791 @default.
- W2017187984 cites W2029573515 @default.
- W2017187984 cites W2030440427 @default.
- W2017187984 cites W2030488550 @default.
- W2017187984 cites W2032211985 @default.
- W2017187984 cites W2032550506 @default.
- W2017187984 cites W2033595975 @default.
- W2017187984 cites W2040575339 @default.
- W2017187984 cites W2043696829 @default.
- W2017187984 cites W2044901721 @default.
- W2017187984 cites W2053131280 @default.
- W2017187984 cites W2054251966 @default.
- W2017187984 cites W2057623977 @default.
- W2017187984 cites W2059139931 @default.
- W2017187984 cites W2059411043 @default.
- W2017187984 cites W2064016607 @default.
- W2017187984 cites W2066998725 @default.
- W2017187984 cites W2069755589 @default.
- W2017187984 cites W2070204715 @default.
- W2017187984 cites W2070851032 @default.
- W2017187984 cites W2077813812 @default.
- W2017187984 cites W2079446921 @default.
- W2017187984 cites W2088594243 @default.
- W2017187984 cites W2092606584 @default.
- W2017187984 cites W2093613683 @default.
- W2017187984 cites W2093725835 @default.
- W2017187984 cites W2096786080 @default.
- W2017187984 cites W2097799776 @default.
- W2017187984 cites W2098544382 @default.
- W2017187984 cites W2100614336 @default.
- W2017187984 cites W2101329867 @default.
- W2017187984 cites W2102726935 @default.
- W2017187984 cites W2103894337 @default.
- W2017187984 cites W2104830962 @default.
- W2017187984 cites W2106543129 @default.
- W2017187984 cites W2109080255 @default.
- W2017187984 cites W2109439031 @default.
- W2017187984 cites W2110648386 @default.
- W2017187984 cites W2110841878 @default.
- W2017187984 cites W2113230030 @default.
- W2017187984 cites W2114095518 @default.
- W2017187984 cites W2114195503 @default.
- W2017187984 cites W2114951160 @default.
- W2017187984 cites W2119351872 @default.
- W2017187984 cites W2121531763 @default.
- W2017187984 cites W2123326378 @default.
- W2017187984 cites W2124196948 @default.
- W2017187984 cites W2125440931 @default.
- W2017187984 cites W2126298634 @default.
- W2017187984 cites W2129931005 @default.
- W2017187984 cites W2131756681 @default.
- W2017187984 cites W2132630169 @default.