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A Single-Step, High-Dose Selection Scheme Reveals Distinct Mechanisms of Acquired Resistance to Oncogenic Kinase Inhibition in Cancer Cells.

Finn KJ, Martin SE, Settleman J.

Cancer Res. 2020 Jan 1;80(1):79-90. doi: 10.1158/0008-5472.CAN-19-0729. Epub 2019 Oct 22.


Synthetic Lethal Interaction of SHOC2 Depletion with MEK Inhibition in RAS-Driven Cancers.

Sulahian R, Kwon JJ, Walsh KH, Pailler E, Bosse TL, Thaker M, Almanza D, Dempster JM, Pan J, Piccioni F, Dumont N, Gonzalez A, Rennhack J, Nabet B, Bachman JA, Goodale A, Lee Y, Bagul M, Liao R, Navarro A, Yuan TL, Ng RWS, Raghavan S, Gray NS, Tsherniak A, Vazquez F, Root DE, Firestone AJ, Settleman J, Hahn WC, Aguirre AJ.

Cell Rep. 2019 Oct 1;29(1):118-134.e8. doi: 10.1016/j.celrep.2019.08.090.


Adaptive Resistance to Dual BRAF/MEK Inhibition in BRAF-Driven Tumors through Autocrine FGFR Pathway Activation.

Wang VE, Xue JY, Frederick DT, Cao Y, Lin E, Wilson C, Urisman A, Carbone DP, Flaherty KT, Bernards R, Lito P, Settleman J, McCormick F.

Clin Cancer Res. 2019 Dec 1;25(23):7202-7217. doi: 10.1158/1078-0432.CCR-18-2779. Epub 2019 Sep 12.


Systematic identification of cancer cell vulnerabilities to natural killer cell-mediated immune surveillance.

Pech MF, Fong LE, Villalta JE, Chan LJ, Kharbanda S, O'Brien JJ, McAllister FE, Firestone AJ, Jan CH, Settleman J.

Elife. 2019 Aug 27;8. pii: e47362. doi: 10.7554/eLife.47362.


Acquired Resistance of EGFR-Mutated Lung Cancer to Tyrosine Kinase Inhibitor Treatment Promotes PARP Inhibitor Sensitivity.

Marcar L, Bardhan K, Gheorghiu L, Dinkelborg P, Pfäffle H, Liu Q, Wang M, Piotrowska Z, Sequist LV, Borgmann K, Settleman JE, Engelman JA, Hata AN, Willers H.

Cell Rep. 2019 Jun 18;27(12):3422-3432.e4. doi: 10.1016/j.celrep.2019.05.058.


Challenges in validating candidate therapeutic targets in cancer.

Settleman J, Sawyers CL, Hunter T.

Elife. 2018 Feb 8;7. pii: e32402. doi: 10.7554/eLife.32402.


Regulation of autophagy, NF-κB signaling, and cell viability by miR-124 in KRAS mutant mesenchymal-like NSCLC cells.

Mehta AK, Hua K, Whipple W, Nguyen MT, Liu CT, Haybaeck J, Weidhaas J, Settleman J, Singh A.

Sci Signal. 2017 Sep 12;10(496). pii: eaam6291. doi: 10.1126/scisignal.aam6291.


Repression of Stress-Induced LINE-1 Expression Protects Cancer Cell Subpopulations from Lethal Drug Exposure.

Guler GD, Tindell CA, Pitti R, Wilson C, Nichols K, KaiWai Cheung T, Kim HJ, Wongchenko M, Yan Y, Haley B, Cuellar T, Webster J, Alag N, Hegde G, Jackson E, Nance TL, Giresi PG, Chen KB, Liu J, Jhunjhunwala S, Settleman J, Stephan JP, Arnott D, Classon M.

Cancer Cell. 2017 Aug 14;32(2):221-237.e13. doi: 10.1016/j.ccell.2017.07.002. Epub 2017 Aug 3.


A three-drug combination to treat BRAF-mutant cancers.

Firestone AJ, Settleman J.

Nat Med. 2017 Aug 4;23(8):913-914. doi: 10.1038/nm.4382. No abstract available.


Cotargeting of MEK and PDGFR/STAT3 Pathways to Treat Pancreatic Ductal Adenocarcinoma.

Sahu N, Chan E, Chu F, Pham T, Koeppen H, Forrest W, Merchant M, Settleman J.

Mol Cancer Ther. 2017 Sep;16(9):1729-1738. doi: 10.1158/1535-7163.MCT-17-0009. Epub 2017 Jun 15.


Ras-MEK Signaling Mediates a Critical Chk1-Dependent DNA Damage Response in Cancer Cells.

Lee HJ, Cao Y, Pham V, Blackwood E, Wilson C, Evangelista M, Klijn C, Stokoe D, Settleman J.

Mol Cancer Ther. 2017 Apr;16(4):694-704. doi: 10.1158/1535-7163.MCT-16-0504. Epub 2017 Jan 30.


Proline Starvation Induces Unresolved ER Stress and Hinders mTORC1-Dependent Tumorigenesis.

Sahu N, Dela Cruz D, Gao M, Sandoval W, Haverty PM, Liu J, Stephan JP, Haley B, Classon M, Hatzivassiliou G, Settleman J.

Cell Metab. 2016 Nov 8;24(5):753-761. doi: 10.1016/j.cmet.2016.08.008. Epub 2016 Sep 8.


Functional screening implicates miR-371-3p and peroxiredoxin 6 in reversible tolerance to cancer drugs.

Sahu N, Stephan JP, Cruz DD, Merchant M, Haley B, Bourgon R, Classon M, Settleman J.

Nat Commun. 2016 Aug 3;7:12351. doi: 10.1038/ncomms12351.


TORquing metabolic reprogramming in cancer cells.

Pusapati R, Settleman J.

Cell Cycle. 2016 Sep 16;15(18):2387-8. doi: 10.1080/15384101.2016.1204850. Epub 2016 Jun 30. No abstract available.


Reproducible pharmacogenomic profiling of cancer cell line panels.

Haverty PM, Lin E, Tan J, Yu Y, Lam B, Lianoglou S, Neve RM, Martin S, Settleman J, Yauch RL, Bourgon R.

Nature. 2016 May 19;533(7603):333-7. doi: 10.1038/nature17987.


mTORC1-Dependent Metabolic Reprogramming Underlies Escape from Glycolysis Addiction in Cancer Cells.

Pusapati RV, Daemen A, Wilson C, Sandoval W, Gao M, Haley B, Baudy AR, Hatzivassiliou G, Evangelista M, Settleman J.

Cancer Cell. 2016 Apr 11;29(4):548-562. doi: 10.1016/j.ccell.2016.02.018. Epub 2016 Mar 24.


Communication in Drug Development: "Translating" Scientific Discovery.

Settleman J, Cohen RL.

Cell. 2016 Mar 10;164(6):1101-1104. doi: 10.1016/j.cell.2016.02.050.


Cancer: Bet on drug resistance.

Settleman J.

Nature. 2016 Jan 21;529(7586):289-90. doi: 10.1038/nature16863. Epub 2016 Jan 6. No abstract available.


Metabolite profiling stratifies pancreatic ductal adenocarcinomas into subtypes with distinct sensitivities to metabolic inhibitors.

Daemen A, Peterson D, Sahu N, McCord R, Du X, Liu B, Kowanetz K, Hong R, Moffat J, Gao M, Boudreau A, Mroue R, Corson L, O'Brien T, Qing J, Sampath D, Merchant M, Yauch R, Manning G, Settleman J, Hatzivassiliou G, Evangelista M.

Proc Natl Acad Sci U S A. 2015 Aug 11;112(32):E4410-7. doi: 10.1073/pnas.1501605112. Epub 2015 Jul 27.


Transcriptional control of autophagy-lysosome function drives pancreatic cancer metabolism.

Perera RM, Stoykova S, Nicolay BN, Ross KN, Fitamant J, Boukhali M, Lengrand J, Deshpande V, Selig MK, Ferrone CR, Settleman J, Stephanopoulos G, Dyson NJ, Zoncu R, Ramaswamy S, Haas W, Bardeesy N.

Nature. 2015 Aug 20;524(7565):361-5. doi: 10.1038/nature14587. Epub 2015 Jul 13.


Enhancing the antitumor efficacy of a cell-surface death ligand by covalent membrane display.

Nair PM, Flores H, Gogineni A, Marsters S, Lawrence DA, Kelley RF, Ngu H, Sagolla M, Komuves L, Bourgon R, Settleman J, Ashkenazi A.

Proc Natl Acad Sci U S A. 2015 May 5;112(18):5679-84. doi: 10.1073/pnas.1418962112. Epub 2015 Apr 20.


Adapting a drug screening platform to discover associations of molecular targeted radiosensitizers with genomic biomarkers.

Liu Q, Wang M, Kern AM, Khaled S, Han J, Yeap BY, Hong TS, Settleman J, Benes CH, Held KD, Efstathiou JA, Willers H.

Mol Cancer Res. 2015 Apr;13(4):713-20. doi: 10.1158/1541-7786.MCR-14-0570. Epub 2015 Feb 9.


Predicting response to HER2 kinase inhibition.

Settleman J.

Oncotarget. 2015 Jan 20;6(2):588-9.


Differential Effects of Tyrosine Kinase Inhibitors on Normal and Oncogenic EGFR Signaling and Downstream Effectors.

Kim Y, Apetri M, Luo B, Settleman JE, Anderson KS.

Mol Cancer Res. 2015 Apr;13(4):765-74. doi: 10.1158/1541-7786.MCR-14-0326. Epub 2015 Jan 8.


A comprehensive transcriptional portrait of human cancer cell lines.

Klijn C, Durinck S, Stawiski EW, Haverty PM, Jiang Z, Liu H, Degenhardt J, Mayba O, Gnad F, Liu J, Pau G, Reeder J, Cao Y, Mukhyala K, Selvaraj SK, Yu M, Zynda GJ, Brauer MJ, Wu TD, Gentleman RC, Manning G, Yauch RL, Bourgon R, Stokoe D, Modrusan Z, Neve RM, de Sauvage FJ, Settleman J, Seshagiri S, Zhang Z.

Nat Biotechnol. 2015 Mar;33(3):306-12. doi: 10.1038/nbt.3080. Epub 2014 Dec 8.


Metabolic and transcriptional profiling reveals pyruvate dehydrogenase kinase 4 as a mediator of epithelial-mesenchymal transition and drug resistance in tumor cells.

Sun Y, Daemen A, Hatzivassiliou G, Arnott D, Wilson C, Zhuang G, Gao M, Liu P, Boudreau A, Johnson L, Settleman J.

Cancer Metab. 2014 Nov 3;2(1):20. doi: 10.1186/2049-3002-2-20. eCollection 2014.


Overcoming EMT-associated resistance to anti-cancer drugs via Src/FAK pathway inhibition.

Wilson C, Nicholes K, Bustos D, Lin E, Song Q, Stephan JP, Kirkpatrick DS, Settleman J.

Oncotarget. 2014 Sep 15;5(17):7328-41.


AXL inhibition sensitizes mesenchymal cancer cells to antimitotic drugs.

Wilson C, Ye X, Pham T, Lin E, Chan S, McNamara E, Neve RM, Belmont L, Koeppen H, Yauch RL, Ashkenazi A, Settleman J.

Cancer Res. 2014 Oct 15;74(20):5878-90. doi: 10.1158/0008-5472.CAN-14-1009. Epub 2014 Aug 14.


Drug resistance via feedback activation of Stat3 in oncogene-addicted cancer cells.

Lee HJ, Zhuang G, Cao Y, Du P, Kim HJ, Settleman J.

Cancer Cell. 2014 Aug 11;26(2):207-21. doi: 10.1016/j.ccr.2014.05.019. Epub 2014 Jul 24.


Optimizing the treatment of BRAF mutant melanoma.

Settleman J.

Genome Med. 2014 Apr 28;6(4):30. doi: 10.1186/gm547. eCollection 2014.


From cancer genomics to precision oncology--tissue's still an issue.

Cohen RL, Settleman J.

Cell. 2014 Jun 19;157(7):1509-14. doi: 10.1016/j.cell.2014.05.027.


The cancer stem cell marker aldehyde dehydrogenase is required to maintain a drug-tolerant tumor cell subpopulation.

Raha D, Wilson TR, Peng J, Peterson D, Yue P, Evangelista M, Wilson C, Merchant M, Settleman J.

Cancer Res. 2014 Jul 1;74(13):3579-90. doi: 10.1158/0008-5472.CAN-13-3456. Epub 2014 May 8.


Comparative oncogenomics identifies PSMB4 and SHMT2 as potential cancer driver genes.

Lee GY, Haverty PM, Li L, Kljavin NM, Bourgon R, Lee J, Stern H, Modrusan Z, Seshagiri S, Zhang Z, Davis D, Stokoe D, Settleman J, de Sauvage FJ, Neve RM.

Cancer Res. 2014 Jun 1;74(11):3114-26. doi: 10.1158/0008-5472.CAN-13-2683. Epub 2014 Apr 22.


EGFR-mediated chromatin condensation protects KRAS-mutant cancer cells against ionizing radiation.

Wang M, Kern AM, Hülskötter M, Greninger P, Singh A, Pan Y, Chowdhury D, Krause M, Baumann M, Benes CH, Efstathiou JA, Settleman J, Willers H.

Cancer Res. 2014 May 15;74(10):2825-34. doi: 10.1158/0008-5472.CAN-13-3157. Epub 2014 Mar 19.


Targeting aberrant glutathione metabolism to eradicate human acute myelogenous leukemia cells.

Pei S, Minhajuddin M, Callahan KP, Balys M, Ashton JM, Neering SJ, Lagadinou ED, Corbett C, Ye H, Liesveld JL, O'Dwyer KM, Li Z, Shi L, Greninger P, Settleman J, Benes C, Hagen FK, Munger J, Crooks PA, Becker MW, Jordan CT.

J Biol Chem. 2013 Nov 22;288(47):33542-58. doi: 10.1074/jbc.M113.511170. Epub 2013 Oct 2.


EGFR-activating mutations correlate with a Fanconi anemia-like cellular phenotype that includes PARP inhibitor sensitivity.

Pfäffle HN, Wang M, Gheorghiu L, Ferraiolo N, Greninger P, Borgmann K, Settleman J, Benes CH, Sequist LV, Zou L, Willers H.

Cancer Res. 2013 Oct 15;73(20):6254-63. doi: 10.1158/0008-5472.CAN-13-0044. Epub 2013 Aug 21.


TORC1 suppression predicts responsiveness to RAF and MEK inhibition in BRAF-mutant melanoma.

Corcoran RB, Rothenberg SM, Hata AN, Faber AC, Piris A, Nazarian RM, Brown RD, Godfrey JT, Winokur D, Walsh J, Mino-Kenudson M, Maheswaran S, Settleman J, Wargo JA, Flaherty KT, Haber DA, Engelman JA.

Sci Transl Med. 2013 Jul 31;5(196):196ra98. doi: 10.1126/scitranslmed.3005753.


Incomplete inhibition of phosphorylation of 4E-BP1 as a mechanism of primary resistance to ATP-competitive mTOR inhibitors.

Ducker GS, Atreya CE, Simko JP, Hom YK, Matli MR, Benes CH, Hann B, Nakakura EK, Bergsland EK, Donner DB, Settleman J, Shokat KM, Warren RS.

Oncogene. 2014 Mar 20;33(12):1590-600. doi: 10.1038/onc.2013.92. Epub 2013 Apr 1.


Bcl-2/Bcl-xL inhibition increases the efficacy of MEK inhibition alone and in combination with PI3 kinase inhibition in lung and pancreatic tumor models.

Tan N, Wong M, Nannini MA, Hong R, Lee LB, Price S, Williams K, Savy PP, Yue P, Sampath D, Settleman J, Fairbrother WJ, Belmont LD.

Mol Cancer Ther. 2013 Jun;12(6):853-64. doi: 10.1158/1535-7163.MCT-12-0949. Epub 2013 Mar 8.


High heregulin expression is associated with activated HER3 and may define an actionable biomarker in patients with squamous cell carcinomas of the head and neck.

Shames DS, Carbon J, Walter K, Jubb AM, Kozlowski C, Januario T, Do A, Fu L, Xiao Y, Raja R, Jiang B, Malekafzali A, Stern H, Settleman J, Wilson TR, Hampton GM, Yauch RL, Pirzkall A, Amler LC.

PLoS One. 2013;8(2):e56765. doi: 10.1371/journal.pone.0056765. Epub 2013 Feb 28. Erratum in: PLoS One. 2013;8(6). doi:10.1371/annotation/63f57c72-c869-4ef5-94d1-3cbd6c2e3678. AnDo [corrected to Do, An].


Synthetic lethal interaction of combined BCL-XL and MEK inhibition promotes tumor regressions in KRAS mutant cancer models.

Corcoran RB, Cheng KA, Hata AN, Faber AC, Ebi H, Coffee EM, Greninger P, Brown RD, Godfrey JT, Cohoon TJ, Song Y, Lifshits E, Hung KE, Shioda T, Dias-Santagata D, Singh A, Settleman J, Benes CH, Mino-Kenudson M, Wong KK, Engelman JA.

Cancer Cell. 2013 Jan 14;23(1):121-8. doi: 10.1016/j.ccr.2012.11.007. Epub 2012 Dec 13.


Noncovalent wild-type-sparing inhibitors of EGFR T790M.

Lee HJ, Schaefer G, Heffron TP, Shao L, Ye X, Sideris S, Malek S, Chan E, Merchant M, La H, Ubhayakar S, Yauch RL, Pirazzoli V, Politi K, Settleman J.

Cancer Discov. 2013 Feb;3(2):168-81. doi: 10.1158/2159-8290.CD-12-0357. Epub 2012 Dec 10.


Genome and transcriptome sequencing of lung cancers reveal diverse mutational and splicing events.

Liu J, Lee W, Jiang Z, Chen Z, Jhunjhunwala S, Haverty PM, Gnad F, Guan Y, Gilbert HN, Stinson J, Klijn C, Guillory J, Bhatt D, Vartanian S, Walter K, Chan J, Holcomb T, Dijkgraaf P, Johnson S, Koeman J, Minna JD, Gazdar AF, Stern HM, Hoeflich KP, Wu TD, Settleman J, de Sauvage FJ, Gentleman RC, Neve RM, Stokoe D, Modrusan Z, Seshagiri S, Shames DS, Zhang Z.

Genome Res. 2012 Dec;22(12):2315-27. doi: 10.1101/gr.140988.112. Epub 2012 Oct 2.


Response to inhibition of smoothened in diverse epithelial cancer cells that lack smoothened or patched 1 mutations.

Galimberti F, Busch AM, Chinyengetere F, Ma T, Sekula D, Memoli VA, Dragnev KH, Liu F, Johnson KC, Guo Y, Freemantle SJ, Andrew AS, Greninger P, Robbins DJ, Settleman J, Benes C, Dmitrovsky E.

Int J Oncol. 2012 Nov;41(5):1751-61. doi: 10.3892/ijo.2012.1599. Epub 2012 Aug 22.


Mechanisms of acquired resistance to targeted cancer therapies.

Lackner MR, Wilson TR, Settleman J.

Future Oncol. 2012 Aug;8(8):999-1014. doi: 10.2217/fon.12.86. Review.


A phase I study of erlotinib and hydroxychloroquine in advanced non-small-cell lung cancer.

Goldberg SB, Supko JG, Neal JW, Muzikansky A, Digumarthy S, Fidias P, Temel JS, Heist RS, Shaw AT, McCarthy PO, Lynch TJ, Sharma S, Settleman JE, Sequist LV.

J Thorac Oncol. 2012 Oct;7(10):1602-8. doi: 10.1097/JTO.0b013e318262de4a.


Widespread potential for growth-factor-driven resistance to anticancer kinase inhibitors.

Wilson TR, Fridlyand J, Yan Y, Penuel E, Burton L, Chan E, Peng J, Lin E, Wang Y, Sosman J, Ribas A, Li J, Moffat J, Sutherlin DP, Koeppen H, Merchant M, Neve R, Settleman J.

Nature. 2012 Jul 26;487(7408):505-9. doi: 10.1038/nature11249.


Temporal resolution of autophosphorylation for normal and oncogenic forms of EGFR and differential effects of gefitinib.

Kim Y, Li Z, Apetri M, Luo B, Settleman JE, Anderson KS.

Biochemistry. 2012 Jun 26;51(25):5212-22. doi: 10.1021/bi300476v. Epub 2012 Jun 13.


Interaction of the EGFR inhibitors gefitinib, vandetanib, pelitinib and neratinib with the ABCG2 multidrug transporter: implications for the emergence and reversal of cancer drug resistance.

Hegedüs C, Truta-Feles K, Antalffy G, Várady G, Német K, Ozvegy-Laczka C, Kéri G, Orfi L, Szakács G, Settleman J, Váradi A, Sarkadi B.

Biochem Pharmacol. 2012 Aug 1;84(3):260-7. doi: 10.1016/j.bcp.2012.04.010. Epub 2012 Apr 21.


Systematic identification of genomic markers of drug sensitivity in cancer cells.

Garnett MJ, Edelman EJ, Heidorn SJ, Greenman CD, Dastur A, Lau KW, Greninger P, Thompson IR, Luo X, Soares J, Liu Q, Iorio F, Surdez D, Chen L, Milano RJ, Bignell GR, Tam AT, Davies H, Stevenson JA, Barthorpe S, Lutz SR, Kogera F, Lawrence K, McLaren-Douglas A, Mitropoulos X, Mironenko T, Thi H, Richardson L, Zhou W, Jewitt F, Zhang T, O'Brien P, Boisvert JL, Price S, Hur W, Yang W, Deng X, Butler A, Choi HG, Chang JW, Baselga J, Stamenkovic I, Engelman JA, Sharma SV, Delattre O, Saez-Rodriguez J, Gray NS, Settleman J, Futreal PA, Haber DA, Stratton MR, Ramaswamy S, McDermott U, Benes CH.

Nature. 2012 Mar 28;483(7391):570-5. doi: 10.1038/nature11005.

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