{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,31]],"date-time":"2026-10-31T03:45:58Z","timestamp":1793418358258,"version":"4.5.0"},"reference-count":60,"publisher":"Springer Science and Business Media LLC","issue":"4","license":[{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T00:00:00Z","timestamp":1551657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Med"],"published-print":{"date-parts":[[2019,4]]},"DOI":"10.1038\/s41591-019-0368-8","type":"journal-article","created":{"date-parts":[[2019,3,4]],"date-time":"2019-03-04T12:04:15Z","timestamp":1551701055000},"page":"628-640","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":630,"title":["Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer"],"prefix":"10.1038","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4026-0942","authenticated-orcid":false,"given":"Kirsten L.","family":"Bryant","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0570-4416","authenticated-orcid":false,"given":"Clint A.","family":"Stalnecker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Zeitouni","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jennifer E.","family":"Klomp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sen","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrey P.","family":"Tikunov","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Venugopal","family":"Gunda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mariaelena","family":"Pierobon","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6058-5878","authenticated-orcid":false,"given":"Andrew M.","family":"Waters","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Samuel D.","family":"George","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Garima","family":"Tomar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8156-7508","authenticated-orcid":false,"given":"Bj\u00f6rn","family":"Papke","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4751-9681","authenticated-orcid":false,"given":"G. Aaron","family":"Hobbs","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tikvah K.","family":"Hayes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J. Nathaniel","family":"Diehl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gennifer D.","family":"Goode","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nina V.","family":"Chaika","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yingxue","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guo-Fang","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agnieszka K.","family":"Witkiewicz","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erik S.","family":"Knudsen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"suffix":"III","given":"Emanuel F.","family":"Petricoin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pankaj K.","family":"Singh","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey M.","family":"Macdonald","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nhan L.","family":"Tran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9309-6141","authenticated-orcid":false,"given":"Costas A.","family":"Lyssiotis","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoqiang","family":"Ying","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alec C.","family":"Kimmelman","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne D.","family":"Cox","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7751-2747","authenticated-orcid":false,"given":"Channing J.","family":"Der","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2019,3,4]]},"reference":[{"key":"368_CR1","doi-asserted-by":"publisher","first-page":"437","DOI":"10.1016\/S1535-6108(03)00309-X","volume":"4","author":"SR Hingorani","year":"2003","unstructured":"Hingorani, S. R. et al. Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse. Cancer Cell. 4, 437\u2013450 (2003).","journal-title":"Cancer Cell."},{"key":"368_CR2","doi-asserted-by":"publisher","first-page":"639","DOI":"10.1172\/JCI59227","volume":"122","author":"MA Collins","year":"2012","unstructured":"Collins, M. A. et al. Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice. J. Clin. Invest. 122, 639\u2013653 (2012).","journal-title":"J. Clin. Invest."},{"key":"368_CR3","doi-asserted-by":"publisher","first-page":"656","DOI":"10.1016\/j.cell.2012.01.058","volume":"149","author":"H Ying","year":"2012","unstructured":"Ying, H. et al. Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism. Cell 149, 656\u2013670 (2012).","journal-title":"Cell"},{"key":"368_CR4","doi-asserted-by":"publisher","first-page":"2140","DOI":"10.1056\/NEJMra1404198","volume":"371","author":"DP Ryan","year":"2014","unstructured":"Ryan, D. P., Hong, T. S. & Bardeesy, N. Pancreatic adenocarcinoma. N. Engl. J. Med. 371, 2140\u20132141 (2014).","journal-title":"N. Engl. J. Med."},{"key":"368_CR5","doi-asserted-by":"publisher","first-page":"a031435","DOI":"10.1101\/cshperspect.a031435","volume":"8","author":"AM Waters","year":"2017","unstructured":"Waters, A. M. & Der, C. J. KRAS: The critical driver and therapeutic target for pancreatic cancer. Cold Spring Harb. Perspect. Med. 8, a031435 (2017).","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"368_CR6","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1038\/nrd4389","volume":"13","author":"AD Cox","year":"2014","unstructured":"Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J. & Der, C. J. Drugging the undruggable RAS: mission possible? Nat. Rev. Drug. Discov. 13, 828\u2013851 (2014).","journal-title":"Nat. Rev. Drug. Discov."},{"key":"368_CR7","doi-asserted-by":"publisher","first-page":"1158","DOI":"10.1126\/science.aam7622","volume":"355","author":"B Papke","year":"2017","unstructured":"Papke, B. & Der, C. J. Drugging RAS: know the enemy. Science 355, 1158\u20131163 (2017).","journal-title":"Science"},{"key":"368_CR8","doi-asserted-by":"publisher","first-page":"272","DOI":"10.1016\/j.ccr.2014.02.017","volume":"25","author":"AG Stephen","year":"2014","unstructured":"Stephen, A. G., Esposito, D., Bagni, R. K. & McCormick, F. Dragging ras back in the ring. Cancer Cell. 25, 272\u2013281 (2014).","journal-title":"Cancer Cell."},{"key":"368_CR9","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.tibs.2013.12.004","volume":"39","author":"KL Bryant","year":"2014","unstructured":"Bryant, K. L., Mancias, J. D., Kimmelman, A. C. & Der, C. J. KRAS: feeding pancreatic cancer proliferation. Trends. Biochem. Sci. 39, 91\u2013100 (2014).","journal-title":"Trends. Biochem. Sci."},{"key":"368_CR10","doi-asserted-by":"publisher","first-page":"1828","DOI":"10.1158\/1078-0432.CCR-14-2425","volume":"21","author":"AC Kimmelman","year":"2015","unstructured":"Kimmelman, A. C. Metabolic dependencies in RAS-driven cancers. Clin. Cancer Res. 21, 1828\u20131834 (2015).","journal-title":"Clin. Cancer Res."},{"key":"368_CR11","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1101\/sqb.2016.81.030981","volume":"81","author":"JY Guo","year":"2016","unstructured":"Guo, J. Y. & White, E. Autophagy, metabolism, and cancer. Cold Spring Harb. Symp. Quant. Biol. 81, 73\u201378 (2016).","journal-title":"Cold Spring Harb. Symp. Quant. Biol."},{"key":"368_CR12","doi-asserted-by":"publisher","first-page":"717","DOI":"10.1101\/gad.2016111","volume":"25","author":"S Yang","year":"2011","unstructured":"Yang, S. et al. Pancreatic cancers require autophagy for tumor growth. Genes Dev. 25, 717\u2013729 (2011).","journal-title":"Genes Dev."},{"key":"368_CR13","doi-asserted-by":"publisher","first-page":"905","DOI":"10.1158\/2159-8290.CD-14-0362","volume":"4","author":"A Yang","year":"2014","unstructured":"Yang, A. et al. Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations. Cancer Discov. 4, 905\u2013913 (2014).","journal-title":"Cancer Discov."},{"key":"368_CR14","doi-asserted-by":"publisher","first-page":"637","DOI":"10.1634\/theoncologist.2014-0086","volume":"19","author":"BM Wolpin","year":"2014","unstructured":"Wolpin, B. M. et al. Phase II and pharmacodynamic study of autophagy inhibition using hydroxychloroquine in patients with metastatic pancreatic adenocarcinoma. Oncologist 19, 637\u2013638 (2014).","journal-title":"Oncologist"},{"key":"368_CR15","doi-asserted-by":"publisher","first-page":"4402","DOI":"10.1245\/s10434-015-4566-4","volume":"22","author":"BA Boone","year":"2015","unstructured":"Boone, B. A. et al. Safety and biologic response of pre-operative autophagy inhibition in combination with gemcitabine in patients with pancreatic adenocarcinoma. Ann. Surg. Oncol. 22, 4402\u20134410 (2015).","journal-title":"Ann. Surg. Oncol."},{"key":"368_CR16","first-page":"1","volume":"24","author":"Society of Surgical Oncology 70th Annual Cancer Symposium.","year":"2017","unstructured":"Society of Surgical Oncology 70th Annual Cancer Symposium. Ann. Surg. Oncol. 24, 1\u2013202 (2017).","journal-title":"Ann. Surg. Oncol."},{"key":"368_CR17","doi-asserted-by":"publisher","first-page":"5295","DOI":"10.1038\/onc.2016.70","volume":"35","author":"S Sanduja","year":"2016","unstructured":"Sanduja, S. et al. AMPK promotes tolerance to Ras pathway inhibition by activating autophagy. Oncogene 35, 5295\u20135303 (2016).","journal-title":"Oncogene"},{"key":"368_CR18","doi-asserted-by":"publisher","first-page":"1406","DOI":"10.1172\/JCI70454","volume":"124","author":"XH Ma","year":"2014","unstructured":"Ma, X. H. et al. Targeting ER stress-induced autophagy overcomes BRAF inhibitor resistance in melanoma. J. Clin. Invest. 124, 1406\u20131417 (2014).","journal-title":"J. Clin. Invest."},{"key":"368_CR19","doi-asserted-by":"publisher","first-page":"628","DOI":"10.1038\/nature13611","volume":"514","author":"A Viale","year":"2014","unstructured":"Viale, A. et al. Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function. Nature 514, 628\u2013632 (2014).","journal-title":"Nature"},{"key":"368_CR20","doi-asserted-by":"publisher","first-page":"460","DOI":"10.1101\/gad.2016311","volume":"25","author":"JY Guo","year":"2011","unstructured":"Guo, J. Y. et al. Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis. Genes Dev. 25, 460\u2013470 (2011).","journal-title":"Genes Dev."},{"key":"368_CR21","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1080\/15548627.2015.1100356","volume":"12","author":"DJ Klionsky","year":"2016","unstructured":"Klionsky, D. J. et al. Guidelines for the use and interpretation of assays for monitoring autophagy (3rd edition). Autophagy. 12, 1\u2013222 (2016).","journal-title":"Autophagy."},{"key":"368_CR22","doi-asserted-by":"publisher","first-page":"2805","DOI":"10.1242\/jcs.01131","volume":"117","author":"Y Kabeya","year":"2004","unstructured":"Kabeya, Y. et al. LC3, GABARAP and GATE16 localize to autophagosomal membrane depending on form-II formation. J. Cell. Sci. 117, 2805\u20132812 (2004).","journal-title":"J. Cell. Sci."},{"key":"368_CR23","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.ccell.2015.11.011","volume":"29","author":"TK Hayes","year":"2016","unstructured":"Hayes, T. K. et al. Long-term ERK inhibition in KRAS-mutant pancreatic cancer is associated with MYC degradation and senescence-like growth suppression. Cancer Cell 29, 75\u201389 (2016).","journal-title":"Cancer Cell"},{"key":"368_CR24","doi-asserted-by":"publisher","first-page":"578","DOI":"10.1016\/j.cell.2018.01.006","volume":"172","author":"MR Janes","year":"2018","unstructured":"Janes, M. R. et al. Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor. Cell 172, 578\u2013589 e517 (2018).","journal-title":"Cell"},{"key":"368_CR25","doi-asserted-by":"publisher","first-page":"2065","DOI":"10.1101\/gad.228122.113","volume":"27","author":"E White","year":"2013","unstructured":"White, E. Exploiting the bad eating habits of Ras-driven cancers. Genes Dev. 27, 2065\u20132071 (2013).","journal-title":"Genes Dev."},{"key":"368_CR26","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2105-14-7","volume":"14","author":"S Hanzelmann","year":"2013","unstructured":"Hanzelmann, S., Castelo, R. & Guinney, J. GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics 14, 7 (2013).","journal-title":"BMC Bioinformatics"},{"key":"368_CR27","doi-asserted-by":"publisher","first-page":"2098","DOI":"10.1158\/0008-5472.CAN-06-3752","volume":"67","author":"PM Campbell","year":"2007","unstructured":"Campbell, P. M. et al. K-Ras promotes growth transformation and invasion of immortalized human pancreatic cells by Raf and phosphatidylinositol 3-kinase signaling. Cancer Res. 67, 2098\u20132106 (2007).","journal-title":"Cancer Res."},{"key":"368_CR28","doi-asserted-by":"publisher","first-page":"742","DOI":"10.1158\/2159-8290.CD-13-0070","volume":"3","author":"EJ Morris","year":"2013","unstructured":"Morris, E. J. et al. Discovery of a novel ERK inhibitor with activity in models of acquired resistance to BRAF and MEK inhibitors. Cancer Discov. 3, 742\u2013750 (2013).","journal-title":"Cancer Discov."},{"key":"368_CR29","doi-asserted-by":"crossref","unstructured":"Moschos, S. J. et al. Development of MK-8353, an orally administered ERK1\/2 inhibitor, in patients with advanced solid tumors. JCI Insight 3, 92352 (2018).","DOI":"10.1172\/jci.insight.92352"},{"key":"368_CR30","doi-asserted-by":"publisher","first-page":"300","DOI":"10.1158\/2159-8290.CD-15-0896","volume":"6","author":"SH Chen","year":"2016","unstructured":"Chen, S. H. et al. Oncogenic BRAF deletions that function as homodimers and are sensitive to inhibition by RAF dimer inhibitor LY3009120. Cancer Discov. 6, 300\u2013315 (2016).","journal-title":"Cancer Discov."},{"key":"368_CR31","doi-asserted-by":"publisher","first-page":"477","DOI":"10.1016\/j.ccell.2016.02.010","volume":"29","author":"SA Foster","year":"2016","unstructured":"Foster, S. A. et al. Activation mechanism of oncogenic deletion mutations in BRAF, EGFR, and HER2. Cancer Cell. 29, 477\u2013493 (2016).","journal-title":"Cancer Cell."},{"key":"368_CR32","doi-asserted-by":"publisher","first-page":"676","DOI":"10.1158\/1541-7786.MCR-12-0690","volume":"11","author":"G Federici","year":"2013","unstructured":"Federici, G. et al. Systems analysis of the NCI-60 cancer cell lines by alignment of protein pathway activation modules with \u201c-OMIC\u201d data fields and therapeutic response signatures. Mol. Cancer Res. 11, 676\u2013685 (2013).","journal-title":"Mol. Cancer Res."},{"key":"368_CR33","doi-asserted-by":"publisher","first-page":"132","DOI":"10.1038\/ncb2152","volume":"13","author":"J Kim","year":"2011","unstructured":"Kim, J., Kundu, M., Viollet, B. & Guan, K. L. AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1. Nat. Cell Biol. 13, 132\u2013141 (2011).","journal-title":"Nat. Cell Biol."},{"key":"368_CR34","doi-asserted-by":"publisher","first-page":"537","DOI":"10.1016\/j.molcel.2015.01.002","volume":"57","author":"JA Kashatus","year":"2015","unstructured":"Kashatus, J. A. et al. Erk2 phosphorylation of Drp1 promotes mitochondrial fission and MAPK-driven tumor growth. Mol. Cell 57, 537\u2013551 (2015).","journal-title":"Mol. Cell"},{"key":"368_CR35","doi-asserted-by":"publisher","first-page":"521","DOI":"10.1016\/j.molcel.2015.01.003","volume":"57","author":"MN Serasinghe","year":"2015","unstructured":"Serasinghe, M. N. et al. Mitochondrial division is requisite to RAS-induced transformation and targeted by oncogenic MAPK pathway inhibitors. Mol. Cell 57, 521\u2013536 (2015).","journal-title":"Mol. Cell"},{"key":"368_CR36","doi-asserted-by":"publisher","first-page":"135","DOI":"10.3389\/fonc.2016.00135","volume":"6","author":"AA Shestov","year":"2016","unstructured":"Shestov, A. A. et al. (13)C MRS and LC-MS flux analysis of tumor intermediary metabolism. Front. Oncol. 6, 135 (2016).","journal-title":"Front. Oncol."},{"key":"368_CR37","doi-asserted-by":"publisher","first-page":"3217","DOI":"10.1158\/0008-5472.CAN-16-3304","volume":"77","author":"K Tech","year":"2017","unstructured":"Tech, K. et al. Pyruvate kinase inhibits proliferation during postnatal cerebellar neurogenesis and suppresses medulloblastoma formation. Cancer Res. 77, 3217\u20133230 (2017).","journal-title":"Cancer Res."},{"key":"368_CR38","doi-asserted-by":"publisher","first-page":"184","DOI":"10.1158\/2159-8290.CD-17-1119","volume":"8","author":"RJ Sullivan","year":"2018","unstructured":"Sullivan, R. J. et al. First-in-class ERK1\/2 inhibitor ulixertinib (BVD-523) in patients with MAPK putant advanced solid tumors: results of a Phase I dose-escalation and expansion study. Cancer Discov. 8, 184\u2013195 (2018).","journal-title":"Cancer Discov."},{"key":"368_CR39","doi-asserted-by":"publisher","first-page":"1344","DOI":"10.1126\/science.1193497","volume":"330","author":"JD Rabinowitz","year":"2010","unstructured":"Rabinowitz, J. D. & White, E. Autophagy and metabolism. Science 330, 1344\u20131348 (2010).","journal-title":"Science"},{"key":"368_CR40","unstructured":"Egan, D. F. Small molecule inhibition of the autophagy kinase ULK1 and identification of ULK1 substrates. Mol. Cell 59, 285\u2013297 (2015)."},{"key":"368_CR41","doi-asserted-by":"publisher","first-page":"11376","DOI":"10.1074\/jbc.C114.627778","volume":"290","author":"KJ Petherick","year":"2015","unstructured":"Petherick, K. J. et al. Pharmacological inhibition of ULK1 kinase blocks mammalian target of rapamycin (mTOR)-dependent autophagy. J. Biol. Chem. 290, 11376\u201311383 (2015).","journal-title":"J. Biol. Chem."},{"key":"368_CR42","doi-asserted-by":"publisher","first-page":"223","DOI":"10.1016\/j.cell.2011.08.037","volume":"147","author":"J Liu","year":"2011","unstructured":"Liu, J. et al. Beclin1 controls the levels of p53 by regulating the deubiquitination activity of USP10 and USP13. Cell 147, 223\u2013234 (2011).","journal-title":"Cell"},{"key":"368_CR43","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1038\/nature12138","volume":"497","author":"C Commisso","year":"2013","unstructured":"Commisso, C. et al. Macropinocytosis of protein is an amino acid supply route in Ras-transformed cells. Nature 497, 633\u2013637 (2013).","journal-title":"Nature"},{"key":"368_CR44","doi-asserted-by":"publisher","first-page":"261","DOI":"10.1016\/j.tibs.2016.01.001","volume":"41","author":"S Cogliati","year":"2016","unstructured":"Cogliati, S., Enriquez, J. A. & Scorrano, L. Mitochondrial cristae: where beauty meets functionality. Trends. Biochem. Sci. 41, 261\u2013273 (2016).","journal-title":"Trends. Biochem. Sci."},{"key":"368_CR45","doi-asserted-by":"publisher","first-page":"5793","DOI":"10.1158\/1078-0432.CCR-11-0341","volume":"17","author":"I Garrido-Laguna","year":"2011","unstructured":"Garrido-Laguna, I. et al. Tumor engraftment in nude mice and enrichment in stroma- related gene pathways predict poor survival and resistance to gemcitabine in patients with pancreatic cancer. Clin. Cancer Res. 17, 5793\u20135800 (2011).","journal-title":"Clin. Cancer Res."},{"key":"368_CR46","doi-asserted-by":"publisher","first-page":"1112","DOI":"10.1158\/2159-8290.CD-18-0349","volume":"8","author":"H Tiriac","year":"2018","unstructured":"Tiriac, H. et al. Organoid profiling identifies common responders to chemotherapy in pancreatic cancer. Cancer Discov. 8, 1112\u20131129 (2018).","journal-title":"Cancer Discov."},{"key":"368_CR47","doi-asserted-by":"crossref","unstructured":"Kinsey, C. G. et al. Protective autophagy elicited by RAF\u2192MEK\u2192ERK inhibition suggests a treatment strategy for RAS-driven cancers. Nat. Med. \n                  http:\/\/doi.org\/10.1038\/s41591-019-0367-9\n                  \n                 (2019).","DOI":"10.1038\/s41591-019-0367-9"},{"key":"368_CR48","doi-asserted-by":"publisher","first-page":"173","DOI":"10.1038\/embor.2008.238","volume":"10","author":"EN N\u2019Diaye","year":"2009","unstructured":"N\u2019Diaye, E. N. et al. PLIC proteins or ubiquilins regulate autophagy-dependent cell survival during nutrient starvation. EMBO Rep. 10, 173\u2013179 (2009).","journal-title":"EMBO Rep."},{"key":"368_CR49","doi-asserted-by":"crossref","unstructured":"Rojansky, R., Cha, M. Y. & Chan, D. C. Elimination of paternal mitochondria in mouse embryos occurs through autophagic degradation dependent on PARKIN and MUL1. Elife 5, e17896 (2016).","DOI":"10.7554\/eLife.17896"},{"key":"368_CR50","doi-asserted-by":"publisher","first-page":"182","DOI":"10.1038\/nprot.2014.004","volume":"9","author":"C Commisso","year":"2014","unstructured":"Commisso, C., Flinn, R. J. & Bar-Sagi, D. Determining the macropinocytic index of cells through a quantitative image-based assay. Nat. Protoc. 9, 182\u2013192 (2014).","journal-title":"Nat. Protoc."},{"key":"368_CR51","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1007\/978-1-4939-6990-6_11","volume":"1606","author":"E Baldelli","year":"2017","unstructured":"Baldelli, E. et al. Reverse phase protein microarrays. Methods Mol. Biol. 1606, 149\u2013169 (2017).","journal-title":"Methods Mol. Biol."},{"key":"368_CR52","doi-asserted-by":"publisher","first-page":"4919","DOI":"10.1158\/1078-0432.CCR-16-2656","volume":"23","author":"M Pierobon","year":"2017","unstructured":"Pierobon, M. et al. Enrichment of PI3K-AKT-mTOR pathway activation in hepatic metastases from breast cancer. Clin. Cancer Res. 23, 4919\u20134928 (2017).","journal-title":"Clin. Cancer Res."},{"key":"368_CR53","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1007\/978-1-60327-216-2_10","volume":"823","author":"M Signore","year":"2012","unstructured":"Signore, M. & Reeder, K. A. Antibody validation by western blotting. Methods Mol. Biol. 823, 139\u2013155 (2012).","journal-title":"Methods Mol. Biol."},{"key":"368_CR54","doi-asserted-by":"publisher","first-page":"32368","DOI":"10.18632\/oncotarget.5941","volume":"6","author":"E Baldelli","year":"2015","unstructured":"Baldelli, E. et al. Functional signaling pathway analysis of lung adenocarcinomas identifies novel therapeutic targets for KRAS mutant tumors. Oncotarget 6, 32368\u201332379 (2015).","journal-title":"Oncotarget"},{"key":"368_CR55","doi-asserted-by":"publisher","first-page":"1294","DOI":"10.1093\/bioinformatics\/bts127","volume":"28","author":"P Millard","year":"2012","unstructured":"Millard, P., Letisse, F., Sokol, S. & Portais, J. C. IsoCor: correcting MS data in isotope labeling experiments. Bioinformatics 28, 1294\u20131296 (2012).","journal-title":"Bioinformatics"},{"key":"368_CR56","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1002\/(SICI)1096-9888(199603)31:3<255::AID-JMS290>3.0.CO;2-3","volume":"31","author":"CA Fernandez","year":"1996","unstructured":"Fernandez, C. A., Des Rosiers, C., Previs, S. F., David, F. & Brunengraber, H. Correction of 13C mass isotopomer distributions for natural stable isotope abundance. J. Mass. Spectrom. 31, 255\u2013262 (1996).","journal-title":"J. Mass. Spectrom."},{"key":"368_CR57","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1016\/j.ab.2010.11.030","volume":"410","author":"K Tomcik","year":"2011","unstructured":"Tomcik, K. et al. Isotopomer enrichment assay for very short chain fatty acids and its metabolic applications. Anal. Biochem. 410, 110\u2013117 (2011).","journal-title":"Anal. Biochem."},{"key":"368_CR58","doi-asserted-by":"publisher","first-page":"95","DOI":"10.1007\/978-1-4939-7665-2_9","volume":"1742","author":"V Gunda","year":"2018","unstructured":"Gunda, V., Kumar, S., Dasgupta, A. & Singh, P. K. Hypoxia-induced metabolomic alterations in pancreatic cancer cells. Methods Mol. Biol. 1742, 95\u2013105 (2018).","journal-title":"Methods Mol. Biol."},{"key":"368_CR59","doi-asserted-by":"publisher","first-page":"71","DOI":"10.1016\/j.ccell.2017.06.004","volume":"32","author":"SK Shukla","year":"2017","unstructured":"Shukla, S. K. et al. MUC1 and HIF-1alpha signaling crosstalk induces anabolic glucose metabolism to impart gemcitabine resistance to pancreatic cancer. Cancer Cell. 32, 71\u201387 e77 (2017).","journal-title":"Cancer Cell."},{"key":"368_CR60","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/j.ccell.2018.10.001","volume":"34","author":"AV Vaseva","year":"2018","unstructured":"Vaseva, A. V. et al. KRAS Suppression-induced degradation of MYC is antagonized by a MEK5-ERK5 compensatory mechanism. Cancer Cell. 34, 807\u2013822 e807 (2018).","journal-title":"Cancer Cell."}],"updated-by":[{"DOI":"10.1038\/s41591-020-0947-8","type":"correction","label":"Correction","source":"publisher","updated":{"date-parts":[[2020,6,1]],"date-time":"2020-06-01T00:00:00Z","timestamp":1590969600000}}],"container-title":["Nature Medicine"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/s41591-019-0368-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41591-019-0368-8","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/s41591-019-0368-8.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,20]],"date-time":"2023-05-20T17:58:45Z","timestamp":1684605525000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/s41591-019-0368-8"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,4]]},"references-count":60,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["368"],"URL":"https:\/\/doi.org\/10.1038\/s41591-019-0368-8","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.735233459.793559653","asserted-by":"object"}]},"ISSN":["1078-8956","1546-170X"],"issn-type":[{"value":"1078-8956","type":"print"},{"value":"1546-170X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,4]]},"assertion":[{"value":"18 June 2018","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"17 January 2019","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"4 March 2019","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"1 June 2020","order":4,"name":"change_date","label":"Change Date","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"Correction","order":5,"name":"change_type","label":"Change Type","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"An amendment to this paper has been published and can be accessed via a link at the top of the paper.","order":6,"name":"change_details","label":"Change Details","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"C.J.D. is on the Scientific Advisory Board of Mirati Therapeutics. A.C.K. has financial interests in Vescor Therapeutics, LLC. A.C.K. is an inventor on patents pertaining to KRAS-regulated metabolic pathways, redox control pathways in pancreatic cancer, targeting GOT1 as a therapeutic approach, and the autophagic control of iron metabolism. A.C.K. is on the Scientific Advisory Board of Cornerstone\/Rafael Pharmaceuticals.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}