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AKT-mTORC1 reactivation is the dominant resistance driver for PI3Kβ/AKT inhibitors in PTEN-null breast cancer and can be overcome by combining with Mcl-1 inhibitors.
Dunn S, Eberlein C, Yu J, Gris-Oliver A, Ong SH, Yelland U, Cureton N, Staniszewska A, McEwen R, Fox M, Pilling J, Hopcroft P, Coker EA, Jaaks P, Garnett MJ, Isherwood B, Serra V, Davies BR, Barry ST, Lynch JT, Yusa K. Dunn S, et al. Among authors: lynch jt. Oncogene. 2022 Nov;41(46):5046-5060. doi: 10.1038/s41388-022-02482-9. Epub 2022 Oct 14. Oncogene. 2022. PMID: 36241868 Free PMC article.
Sensitivity to PI3K and AKT inhibitors is mediated by divergent molecular mechanisms in subtypes of DLBCL.
Erdmann T, Klener P, Lynch JT, Grau M, Vočková P, Molinsky J, Tuskova D, Hudson K, Polanska UM, Grondine M, Mayo M, Dai B, Pfeifer M, Erdmann K, Schwammbach D, Zapukhlyak M, Staiger AM, Ott G, Berdel WE, Davies BR, Cruzalegui F, Trneny M, Lenz P, Barry ST, Lenz G. Erdmann T, et al. Among authors: lynch jt. Blood. 2017 Jul 20;130(3):310-322. doi: 10.1182/blood-2016-12-758599. Epub 2017 Feb 15. Blood. 2017. PMID: 28202458 Free article.
Inhibiting PI3Kβ with AZD8186 Regulates Key Metabolic Pathways in PTEN-Null Tumors.
Lynch JT, Polanska UM, Delpuech O, Hancox U, Trinidad AG, Michopoulos F, Lenaghan C, McEwen R, Bradford J, Polanski R, Ellston R, Avivar-Valderas A, Pilling J, Staniszewska A, Cumberbatch M, Critchlow SE, Cruzalegui F, Barry ST. Lynch JT, et al. Clin Cancer Res. 2017 Dec 15;23(24):7584-7595. doi: 10.1158/1078-0432.CCR-17-0676. Epub 2017 Oct 2. Clin Cancer Res. 2017. PMID: 28972046
Combined Inhibition of PI3Kβ and mTOR Inhibits Growth of PTEN-null Tumors.
Lynch JT, Polanska UM, Hancox U, Delpuech O, Maynard J, Trigwell C, Eberlein C, Lenaghan C, Polanski R, Avivar-Valderas A, Cumberbatch M, Klinowska T, Critchlow SE, Cruzalegui F, Barry ST. Lynch JT, et al. Mol Cancer Ther. 2018 Nov;17(11):2309-2319. doi: 10.1158/1535-7163.MCT-18-0183. Epub 2018 Aug 10. Mol Cancer Ther. 2018. PMID: 30097489
Drug mechanism-of-action discovery through the integration of pharmacological and CRISPR screens.
Gonçalves E, Segura-Cabrera A, Pacini C, Picco G, Behan FM, Jaaks P, Coker EA, van der Meer D, Barthorpe A, Lightfoot H, Mironenko T, Beck A, Richardson L, Yang W, Lleshi E, Hall J, Tolley C, Hall C, Mali I, Thomas F, Morris J, Leach AR, Lynch JT, Sidders B, Crafter C, Iorio F, Fawell S, Garnett MJ. Gonçalves E, et al. Among authors: lynch jt. Mol Syst Biol. 2020 Jul;16(7):e9405. doi: 10.15252/msb.20199405. Mol Syst Biol. 2020. PMID: 32627965 Free PMC article.
Large-scale Pan-cancer Cell Line Screening Identifies Actionable and Effective Drug Combinations.
Bashi AC, Coker EA, Bulusu KC, Jaaks P, Crafter C, Lightfoot H, Milo M, McCarten K, Jenkins DF, van der Meer D, Lynch JT, Barthorpe S, Andersen CL, Barry ST, Beck A, Cidado J, Gordon JA, Hall C, Hall J, Mali I, Mironenko T, Mongeon K, Morris J, Richardson L, Smith PD, Tavana O, Tolley C, Thomas F, Willis BS, Yang W, O'Connor MJ, McDermott U, Critchlow SE, Drew L, Fawell SE, Mettetal JT, Garnett MJ. Bashi AC, et al. Among authors: lynch jt. Cancer Discov. 2024 May 1;14(5):846-865. doi: 10.1158/2159-8290.CD-23-0388. Cancer Discov. 2024. PMID: 38456804 Free PMC article.
Development of a Series of Pyrrolopyridone MAT2A Inhibitors.
Atkinson SJ, Bagal SK, Argyrou A, Askin S, Cheung T, Chiarparin E, Coen M, Collie IT, Dale IL, De Fusco C, Dillman K, Evans L, Feron LJ, Foster AJ, Grondine M, Kantae V, Lamont GM, Lamont S, Lynch JT, Nilsson Lill S, Robb GR, Saeh J, Schimpl M, Scott JS, Smith J, Srinivasan B, Tentarelli S, Vazquez-Chantada M, Wagner D, Walsh JJ, Watson D, Williamson B. Atkinson SJ, et al. Among authors: lynch jt. J Med Chem. 2024 Mar 28;67(6):4541-4559. doi: 10.1021/acs.jmedchem.3c01860. Epub 2024 Mar 11. J Med Chem. 2024. PMID: 38466661
Fragment-Based Design of a Potent MAT2a Inhibitor and in Vivo Evaluation in an MTAP Null Xenograft Model.
De Fusco C, Schimpl M, Börjesson U, Cheung T, Collie I, Evans L, Narasimhan P, Stubbs C, Vazquez-Chantada M, Wagner DJ, Grondine M, Sanders MG, Tentarelli S, Underwood E, Argyrou A, Smith JM, Lynch JT, Chiarparin E, Robb G, Bagal SK, Scott JS. De Fusco C, et al. Among authors: lynch jt. J Med Chem. 2021 May 27;64(10):6814-6826. doi: 10.1021/acs.jmedchem.1c00067. Epub 2021 Apr 26. J Med Chem. 2021. PMID: 33900758 Free article.
69 results