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AssigneeNew York University
InventorsBenjamin G. NEEL, Kwok-Kin WONG, Suman MUKHOPADHYAY, Wei WEI
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This application relates to methods for overcoming or preventing resistance of a KRAS mutant cancer cell to a growth inhibition and/or cell death induction by a KRAS inhibitor or a SHP2 inhibitor, as well as to methods for enhancing sensitivity of a KRAS mutant cancer cell to a KRAS inhibitor or a SHP2 inhibitor. The application further relates to methods of treating a KRAS mutant cancer in a subject, the method comprising administering to the subject an effective amount of a KRAS inhibitor or a SHP2 inhibitor and an inhibitor of expression or function or a degrader or a binding partner of one or more of various proteins described herein. Related pharmaceutical compositions and kits are also disclosed.
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A method for enhancing sensitivity and/or overcoming or preventing resistance of a KRAS mutant cancer cell to a KRAS inhibitor, comprising inhibiting in said KRAS mutant cancer cell expression or function of one or more proteins selected from VRK1, RIOK2, EXT1, EXT2, ELP2, ELP3, ELP5, PKN2, ROCK1, ROCK2, TFIIIC, GTF3C1, TBP, HSD17B10, POP5, RPP21, RTCB, TSEN2, URM1, ELP4, ELP1 (IKBKAP), ADAT3, MOCS3, KTI12, IARS, YARS, SEPSECS, PARS2, YARS2, DARS2, and LARS2.
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A method of treating a KRAS mutant cancer in a subject in need thereof, comprising administering to the subject an effective amount of a KRAS inhibitor and an inhibitor of expression or function or a degrader of one or more proteins selected from VRK1, RIOK2, PKN2, EXT1, EXT2, ELP2, ELP3, ELP5, ROCK1, ROCK2, TFIIIC, GTF3C1, TBP, HSD17B10, POP5, RPP21, RTCB, TSEN2, URM1, ELP4, ELP1 (IKBKAP), ADAT3, MOCS3, KTI12, IARS, YARS, SEPSECS, PARS2, YARS2, DARS2, and LARS2.
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A pharmaceutical composition comprising (i) a KRAS inhibitor, (ii) an inhibitor of expression or function or a degrader of one or more proteins selected from VRK1, RIOK2, PKN2, EXT1, EXT2, ELP2, ELP3, ELP5, ROCK1, ROCK2, TFIIIC, GTF3C1, TBP, HSD17B10, POP5, RPP21, RTCB, TSEN2, URM1, ELP4, ELP1 (IKBKAP), ADAT3, MOCS3, KTI12, IARS, YARS, SEPSECS, PARS2, YARS2, DARS2, and LARS2, and (iii) a pharmaceutically acceptable carrier and/or excipient.
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Dependencies are inferred from the claim text.