{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:20:43Z","timestamp":1792790443975,"version":"4.5.0"},"posted":{"date-parts":[[2026,10,5]]},"group-title":"Cancer Biology","reference-count":124,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T00:00:00Z","timestamp":1791158400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"funder":[{"award":["R01CA272732"],"award-info":[{"award-number":["R01CA272732"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"award":["R01CA266472"],"award-info":[{"award-number":["R01CA266472"]}],"id":[{"id":"https:\/\/ror.org\/040gcmg81","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Lustgarten Foundation-AACR","id":[{"id":"https:\/\/ror.org\/030635250","id-type":"ROR","asserted-by":"crossref"}]},{"name":"Concern Foundation for Cancer Research"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2026,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Treatments for pancreatic ductal adenocarcinoma (PDAC) often fail because of the cancer\u2019s ability to adapt its signaling and metabolic pathways to circumvent treatment mechanisms. PDAC hallmarks that promote treatment resistance (increased fatty acid metabolism, survival signaling, desmoplasia, and macropinocytosis) are extensively regulated by heparan sulfate proteoglycans (HSPGs) and their binding partners. The pro-tumor functions of HSPGs are controlled by site-specific cleavage of their heparan sulfate chains by mammalian heparanase; however, cleavage by bacterial heparinase III (HepIII) represses these functions and prevents downstream, pro-tumor signaling. Using tumor-targeting, attenuated\n                  <jats:italic>Salmonella typhimurium<\/jats:italic>\n                  (strain YS1646), we have limited HepIII transgene expression to tumor tissue. Degradation of tumor cell heparan sulfates by HepIII resulted in decreased macropinocytosis, reduced survival signaling, lipid storage depletion, and decreased expression of translational machinery. This tumor-targeting treatment has the potential to improve the efficacy of several approved pancreatic cancer therapies, which is predicted to increase patient survival.\n                <\/jats:p>","DOI":"10.64898\/2026.10.01.756059","type":"posted-content","created":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:35:14Z","timestamp":1791189314000},"source":"Crossref","is-referenced-by-count":0,"title":["Precision Targeting of Heparan Sulfate Proteoglycans Broadly Dysregulates Survival Signaling and Metabolic Adaptation in Pancreatic Cancer"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1998-3719","authenticated-orcid":false,"given":"Nancy D.","family":"Ebelt","sequence":"first","affiliation":[{"name":"Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2608-5092","authenticated-orcid":false,"given":"Suvithanandhini","family":"Loganathan","sequence":"additional","affiliation":[{"name":"Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-7287-8650","authenticated-orcid":false,"given":"Lara C.","family":"Avsharian","sequence":"additional","affiliation":[{"name":"Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA"},{"name":"Irell and Manella Graduate School of Biological Sciences, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katarzyna","family":"Dabrowska","sequence":"additional","affiliation":[{"name":"Integrated Mass Spectrometry Shared Resource, City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nathaniel","family":"Hansen","sequence":"additional","affiliation":[{"name":"Integrated Mass Spectrometry Shared Resource, City of Hope, Duarte, CA"},{"name":"Early Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8050-0747","authenticated-orcid":false,"given":"Khyatiben V.","family":"Pathak","sequence":"additional","affiliation":[{"name":"Integrated Mass Spectrometry Shared Resource, City of Hope, Duarte, CA"},{"name":"Early Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Patrick","family":"Pirrotte","sequence":"additional","affiliation":[{"name":"Integrated Mass Spectrometry Shared Resource, City of Hope, Duarte, CA"},{"name":"Early Detection and Prevention Division, Translational Genomics Research Institute, Phoenix, AZ"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4602-7060","authenticated-orcid":false,"given":"Edwin R.","family":"Manuel","sequence":"additional","affiliation":[{"name":"Department of Immuno-Oncology, Beckman Research Institute of City of Hope, Duarte, CA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2026100808500827000_2026.10.01.756059v1.1","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1038\/s41392-023-01383-x","article-title":"Tumor cell plasticity in targeted therapy-induced resistance: mechanisms and new strategies","volume":"8","year":"2023","journal-title":"Signal transduction and targeted therapy"},{"key":"2026100808500827000_2026.10.01.756059v1.2","doi-asserted-by":"crossref","unstructured":"M. A. Desbats , I. Giacomini , T. Prayer-Galetti , M. Montopoli , Metabolic Plasticity in Chemotherapy Resistance. Frontiers in Oncology Volume 10 - 2020, (2020).","DOI":"10.3389\/fonc.2020.00281"},{"key":"2026100808500827000_2026.10.01.756059v1.3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1080\/23808993.2020.1730694","article-title":"Nab-paclitaxel and atezolizumab for the treatment of PD-L1-positive, metastatic triple-negative breast cancer: review and future directions","volume":"5","year":"2020","journal-title":"Expert review of precision medicine and drug development"},{"key":"2026100808500827000_2026.10.01.756059v1.4","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1910231"},{"key":"2026100808500827000_2026.10.01.756059v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1408868"},{"key":"2026100808500827000_2026.10.01.756059v1.6","first-page":"496","article-title":"Targeted therapy: resistance and re-sensitization","volume":"34","year":"2015","journal-title":"Chinese journal of cancer"},{"key":"2026100808500827000_2026.10.01.756059v1.7","doi-asserted-by":"crossref","first-page":"188","DOI":"10.1186\/s41065-025-00564-8","article-title":"Cancer cell plasticity and therapeutic resistance: mechanisms, crosstalk, and translational perspectives","volume":"162","year":"2025","journal-title":"Hereditas"},{"key":"2026100808500827000_2026.10.01.756059v1.8","doi-asserted-by":"crossref","unstructured":"S. N\u00e9grier et al., Phase I dose-escalation study of pazopanib combined with bevacizumab in patients with metastatic renal cell carcinoma or other advanced tumors. BMC cancer 17, 547 (2017).","DOI":"10.1186\/s12885-017-3527-7"},{"key":"2026100808500827000_2026.10.01.756059v1.9","doi-asserted-by":"crossref","first-page":"2915","DOI":"10.7314\/APJCP.2015.16.7.2915","article-title":"Meta-analysis of seven randomized control trials to assess the efficacy and toxicity of combining EGFR-TKI with chemotherapy for patients with advanced NSCLC who failed first-line treatment","volume":"16","year":"2015","journal-title":"Asian Pacific journal of cancer prevention : APJCP"},{"key":"2026100808500827000_2026.10.01.756059v1.10","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1002\/ijc.29377","article-title":"Safety profile of combined therapy inhibiting EFGR and VEGF pathways in patients with advanced non-small-cell lung cancer: A meta-analysis of 15 phase II\/III randomized trials","volume":"137","year":"2015","journal-title":"International journal of cancer"},{"key":"2026100808500827000_2026.10.01.756059v1.11","first-page":"223","article-title":"Breast cancer therapy and cardiovascular risk: focus on trastuzumab","volume":"11","year":"2015","journal-title":"Vascular health and risk management"},{"key":"2026100808500827000_2026.10.01.756059v1.12","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-14-0155"},{"key":"2026100808500827000_2026.10.01.756059v1.13","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i32.11241"},{"key":"2026100808500827000_2026.10.01.756059v1.14","unstructured":"P. Bhoopathi , P. Mannangatti , S. K. Das , P. B. Fisher , L. Emdad , in Advances in Cancer Research, L. Emdad , A. Atfi , R. Gogna , J. G. Trevino , P. B. Fisher , Eds. (Academic Press, 2023), vol. 159, pp. 285\u2013341."},{"key":"2026100808500827000_2026.10.01.756059v1.15","doi-asserted-by":"publisher","DOI":"10.1016\/j.annonc.2023.08.009"},{"key":"2026100808500827000_2026.10.01.756059v1.16","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1415606"},{"key":"2026100808500827000_2026.10.01.756059v1.17","doi-asserted-by":"crossref","unstructured":"D. S. Richardson , J. M. Spehar , D. T. Han , P. A. Chakravarthy , S. T. Sizemore , The RAL Enigma: Distinct Roles of RALA and RALB in Cancer. Cells 11, (2022).","DOI":"10.3390\/cells11101645"},{"key":"2026100808500827000_2026.10.01.756059v1.18","doi-asserted-by":"crossref","unstructured":"D. Javadrashid et al., Pancreatic Cancer Signaling Pathways, Genetic Alterations, and Tumor Microenvironment: The Barriers Affecting the Method of Treatment. Biomedicines 9, (2021).","DOI":"10.3390\/biomedicines9040373"},{"key":"2026100808500827000_2026.10.01.756059v1.19","doi-asserted-by":"publisher","DOI":"10.1021\/bi200642e"},{"key":"2026100808500827000_2026.10.01.756059v1.20","doi-asserted-by":"crossref","first-page":"2827","DOI":"10.3390\/cimb46040177","article-title":"Significance of TP53, CDKN2A, SMAD4 and KRAS in Pancreatic Cancer","volume":"46","year":"2024","journal-title":"Curr Issues Mol Biol"},{"key":"2026100808500827000_2026.10.01.756059v1.21","doi-asserted-by":"crossref","unstructured":"M. Ram Makena et al., Wnt\/\u03b2-Catenin Signaling: The Culprit in Pancreatic Carcinogenesis and Therapeutic Resistance. Int J Mol Sci 20, (2019).","DOI":"10.3390\/ijms20174242"},{"key":"2026100808500827000_2026.10.01.756059v1.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2013.03.003"},{"key":"2026100808500827000_2026.10.01.756059v1.23","doi-asserted-by":"crossref","unstructured":"J. Dardare , A. Witz , J. L. Merlin , P. Gilson , A. Harl\u00e9 , SMAD4 and the TGF\u03b2 Pathway in Patients with Pancreatic Ductal Adenocarcinoma. Int J Mol Sci 21, (2020).","DOI":"10.3390\/ijms21103534"},{"key":"2026100808500827000_2026.10.01.756059v1.24","doi-asserted-by":"crossref","unstructured":"M. Mascaraque et al., Fatty acid oxidation is critical for the tumorigenic potential and chemoresistance of pancreatic cancer stem cells. Journal of translational medicine 22, 797 (2024).","DOI":"10.1186\/s12967-024-05598-6"},{"key":"2026100808500827000_2026.10.01.756059v1.25","doi-asserted-by":"crossref","first-page":"2477","DOI":"10.3390\/cancers12092477","article-title":"ATP Production Relies on Fatty Acid Oxidation Rather than Glycolysis in Pancreatic Ductal Adenocarcinoma","volume":"12","year":"2020","journal-title":"Cancers"},{"key":"2026100808500827000_2026.10.01.756059v1.26","doi-asserted-by":"publisher","DOI":"10.3748\/wjg.v20.i9.2279"},{"key":"2026100808500827000_2026.10.01.756059v1.27","doi-asserted-by":"crossref","unstructured":"L. Yan , P. Raj , W. Yao , H. Ying , Glucose Metabolism in Pancreatic Cancer. Cancers 11, (2019).","DOI":"10.3390\/cancers11101460"},{"key":"2026100808500827000_2026.10.01.756059v1.28","doi-asserted-by":"publisher","DOI":"10.1038\/nature12040"},{"key":"2026100808500827000_2026.10.01.756059v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2012.310"},{"key":"2026100808500827000_2026.10.01.756059v1.30","doi-asserted-by":"publisher","DOI":"10.1111\/bph.13616"},{"key":"2026100808500827000_2026.10.01.756059v1.31","doi-asserted-by":"crossref","unstructured":"O. Olivares et al., Collagen-derived proline promotes pancreatic ductal adenocarcinoma cell survival under nutrient limited conditions. Nature Communications 8, 16031 (2017).","DOI":"10.1038\/ncomms16031"},{"key":"2026100808500827000_2026.10.01.756059v1.32","doi-asserted-by":"publisher","DOI":"10.1097\/MPA.0b013e318247d903"},{"key":"2026100808500827000_2026.10.01.756059v1.33","doi-asserted-by":"publisher","DOI":"10.1038\/nature12138"},{"key":"2026100808500827000_2026.10.01.756059v1.34","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-17-1215"},{"key":"2026100808500827000_2026.10.01.756059v1.35","doi-asserted-by":"crossref","first-page":"1121","DOI":"10.1038\/s41467-020-14928-3","article-title":"Macropinocytosis confers resistance to therapies targeting cancer anabolism","volume":"11","year":"2020","journal-title":"Nature Communications"},{"key":"2026100808500827000_2026.10.01.756059v1.36","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2012.01.058"},{"key":"2026100808500827000_2026.10.01.756059v1.37","doi-asserted-by":"crossref","first-page":"4945","DOI":"10.1038\/s41467-018-07472-8","article-title":"Oncogenic KRAS supports pancreatic cancer through regulation of nucleotide synthesis","volume":"9","year":"2018","journal-title":"Nature Communications"},{"key":"2026100808500827000_2026.10.01.756059v1.38","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1985910"},{"key":"2026100808500827000_2026.10.01.756059v1.39","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3114"},{"key":"2026100808500827000_2026.10.01.756059v1.40","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.08.001"},{"key":"2026100808500827000_2026.10.01.756059v1.41","doi-asserted-by":"crossref","unstructured":"J. S. Lee et al., ATP Production Relies on Fatty Acid Oxidation Rather than Glycolysis in Pancreatic Ductal Adenocarcinoma. Cancers 12, (2020).","DOI":"10.3390\/cancers12092477"},{"key":"2026100808500827000_2026.10.01.756059v1.42","doi-asserted-by":"publisher","DOI":"10.1038\/nm.4256"},{"key":"2026100808500827000_2026.10.01.756059v1.43","doi-asserted-by":"crossref","unstructured":"S. Sarrazin , W. C. Lamanna , J. D. Esko , Heparan sulfate proteoglycans. Cold Spring Harbor perspectives in biology 3, (2011).","DOI":"10.1101\/cshperspect.a004952"},{"key":"2026100808500827000_2026.10.01.756059v1.44","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.10.004"},{"key":"2026100808500827000_2026.10.01.756059v1.45","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113738"},{"key":"2026100808500827000_2026.10.01.756059v1.46","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.03.001"},{"key":"2026100808500827000_2026.10.01.756059v1.47","doi-asserted-by":"crossref","unstructured":"X. Sun et al., Elevated heparanase expression is associated with poor prognosis in breast cancer: a study based on systematic review and TCGA data. 8, (2017).","DOI":"10.18632\/oncotarget.16575"},{"key":"2026100808500827000_2026.10.01.756059v1.48","doi-asserted-by":"crossref","unstructured":"K. M. Jayatilleke , M. D. Hulett , Heparanase and the hallmarks of cancer. Journal of translational medicine 18, 453 (2020).","DOI":"10.1186\/s12967-020-02624-1"},{"key":"2026100808500827000_2026.10.01.756059v1.49","doi-asserted-by":"publisher","DOI":"10.1007\/s10456-013-9401-6"},{"key":"2026100808500827000_2026.10.01.756059v1.50","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4652(199803)174:3<310::AID-JCP5>3.0.CO;2-R"},{"key":"2026100808500827000_2026.10.01.756059v1.51","doi-asserted-by":"crossref","first-page":"e54469","DOI":"10.7554\/eLife.54469","article-title":"R-spondins engage heparan sulfate proteoglycans to potentiate WNT signaling","volume":"9","year":"2020","journal-title":"eLife"},{"key":"2026100808500827000_2026.10.01.756059v1.52","doi-asserted-by":"crossref","unstructured":"M. A. Soares et al., Heparan Sulfate Proteoglycans May Promote or Inhibit Cancer Progression by Interacting with Integrins and Affecting Cell Migration. BioMed research international 2015, 453801 (2015).","DOI":"10.1155\/2015\/453801"},{"key":"2026100808500827000_2026.10.01.756059v1.53","doi-asserted-by":"crossref","unstructured":"M. W. Datta et al., Perlecan, a candidate gene for the CAPB locus, regulates prostate cancer cell growth via the Sonic Hedgehog pathway. Molecular cancer 5, 9 (2006).","DOI":"10.1186\/1476-4598-5-9"},{"key":"2026100808500827000_2026.10.01.756059v1.54","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.bcp.2019.06.020","article-title":"Role of glypicans in regulation of the tumor microenvironment and cancer progression","volume":"168","year":"2019","journal-title":"Biochemical Pharmacology"},{"key":"2026100808500827000_2026.10.01.756059v1.55","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1002\/2211-5463.12190","article-title":"Overexpression of heparanase attenuated TGF-\u03b2-stimulated signaling in tumor cells","volume":"7","year":"2017","journal-title":"FEBS Open Bio"},{"key":"2026100808500827000_2026.10.01.756059v1.56","doi-asserted-by":"publisher","DOI":"10.1038\/cr.2015.29"},{"key":"2026100808500827000_2026.10.01.756059v1.57","first-page":"e1047556","article-title":"Heparanase tailors syndecan for exosome production","volume":"3","year":"2015","journal-title":"Mol Cell Oncol"},{"key":"2026100808500827000_2026.10.01.756059v1.58","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2005.07.011"},{"key":"2026100808500827000_2026.10.01.756059v1.59","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M701611200"},{"key":"2026100808500827000_2026.10.01.756059v1.60","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2009.05.002"},{"key":"2026100808500827000_2026.10.01.756059v1.61","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M414546200"},{"key":"2026100808500827000_2026.10.01.756059v1.62","doi-asserted-by":"crossref","first-page":"136","DOI":"10.7164\/antibiotics.57.136","article-title":"Exploitation of heparanase inhibitors from microbial metabolites using an efficient visual screening system","volume":"57","year":"2004","journal-title":"J. Antibiot"},{"key":"2026100808500827000_2026.10.01.756059v1.63","doi-asserted-by":"crossref","unstructured":"R. Leblanc , et al., Pharmacological inhibition of syntenin PDZ2 domain impairs breast cancer cell activities and exosome loading with syndecan and EpCAM cargo. 10, e12039 (2020).","DOI":"10.1002\/jev2.12039"},{"key":"2026100808500827000_2026.10.01.756059v1.64","doi-asserted-by":"crossref","first-page":"354","DOI":"10.1016\/j.ejmech.2018.05.015","article-title":"Syntenin-targeted peptide blocker inhibits progression of cancer cells","volume":"154","year":"2018","journal-title":"Eur. J. Med. Chem"},{"key":"2026100808500827000_2026.10.01.756059v1.65","doi-asserted-by":"crossref","first-page":"1069","DOI":"10.1158\/1535-7163.1069.3.9","article-title":"Structure-based design of a selective heparanase inhibitor as an antimetastatic agent","volume":"3","year":"2004","journal-title":"Mol. Cancer Ther"},{"key":"2026100808500827000_2026.10.01.756059v1.66","doi-asserted-by":"crossref","unstructured":"K. M. Jayatilleke , M. D. Hulett , Heparanase and the hallmarks of cancer. J. Transl. Med. 18, 453 (2020).","DOI":"10.1186\/s12967-020-02624-1"},{"key":"2026100808500827000_2026.10.01.756059v1.67","unstructured":"I. Vlodavsky , in Encyclopedia of Cancer, M. Schwab , Ed. (Springer Berlin Heidelberg, Berlin, Heidelberg, 2009), pp. 1335\u20131339."},{"key":"2026100808500827000_2026.10.01.756059v1.68","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2013.02.006"},{"key":"2026100808500827000_2026.10.01.756059v1.69","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djh230"},{"key":"2026100808500827000_2026.10.01.756059v1.70","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.028498"},{"key":"2026100808500827000_2026.10.01.756059v1.71","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1007\/s12192-018-0955-5","article-title":"Cell surface heparan sulfate proteoglycans are involved in the extracellular Hsp90-stimulated migration and invasion of cancer cells","volume":"24","year":"2019","journal-title":"Cell Stress Chaperones"},{"key":"2026100808500827000_2026.10.01.756059v1.72","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-012-2056-z"},{"key":"2026100808500827000_2026.10.01.756059v1.73","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.4.1524"},{"key":"2026100808500827000_2026.10.01.756059v1.74","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012578299"},{"key":"2026100808500827000_2026.10.01.756059v1.75","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-082495"},{"key":"2026100808500827000_2026.10.01.756059v1.76","doi-asserted-by":"publisher","DOI":"10.1038\/s41568-018-0070-z"},{"key":"2026100808500827000_2026.10.01.756059v1.77","doi-asserted-by":"crossref","first-page":"4765","DOI":"10.7150\/jca.32650","article-title":"Salmonella-Mediated Cancer Therapy: An Innovative Therapeutic Strategy","volume":"10","year":"2019","journal-title":"Journal of Cancer"},{"key":"2026100808500827000_2026.10.01.756059v1.78","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2023.02.010"},{"key":"2026100808500827000_2026.10.01.756059v1.79","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2020.01.080"},{"key":"2026100808500827000_2026.10.01.756059v1.80","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-14928-3"},{"key":"2026100808500827000_2026.10.01.756059v1.81","doi-asserted-by":"publisher","DOI":"10.1128\/jb.177.14.4121-4130.1995"},{"key":"2026100808500827000_2026.10.01.756059v1.82","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.04.055"},{"key":"2026100808500827000_2026.10.01.756059v1.83","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4806"},{"key":"2026100808500827000_2026.10.01.756059v1.84","doi-asserted-by":"publisher","DOI":"10.1159\/000085702"},{"key":"2026100808500827000_2026.10.01.756059v1.85","doi-asserted-by":"crossref","unstructured":"S. Kind et al., Prevalence of Syndecan-1 (CD138) Expression in Different Kinds of Human Tumors and Normal Tissues. Disease Markers 2019, 4928315 (2019).","DOI":"10.1155\/2019\/4928315"},{"key":"2026100808500827000_2026.10.01.756059v1.86","first-page":"3228","volume":"13","year":"2021","journal-title":"Integration of Salmonella into Combination Cancer Therapy"},{"key":"2026100808500827000_2026.10.01.756059v1.87","first-page":"3057","article-title":"Salmonella cancer therapy metabolically disrupts tumours at the collateral cost of T cell immunity","volume":"16","year":"2024","journal-title":"EMBO molecular medicine"},{"key":"2026100808500827000_2026.10.01.756059v1.88","first-page":"755","volume":"102","year":"2005","journal-title":"Tumor-targeting bacterial therapy with amino acid auxotrophs of GFP-expressing Salmonella typhimurium"},{"key":"2026100808500827000_2026.10.01.756059v1.89","doi-asserted-by":"crossref","first-page":"930","DOI":"10.3892\/ol.2016.5500","article-title":"Regulation of cell migration via the EGFR signaling pathway in oral squamous cell carcinoma cells","volume":"13","year":"2017","journal-title":"Oncology letters"},{"key":"2026100808500827000_2026.10.01.756059v1.90","doi-asserted-by":"publisher","DOI":"10.1038\/sj.bjc.6604473"},{"key":"2026100808500827000_2026.10.01.756059v1.91","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.21145"},{"key":"2026100808500827000_2026.10.01.756059v1.92","doi-asserted-by":"crossref","first-page":"13443","DOI":"10.3390\/ijms252413443","article-title":"Regulation of Cancer Metastasis by PAK2","volume":"25","year":"2024","journal-title":"International Journal of Molecular Sciences"},{"key":"2026100808500827000_2026.10.01.756059v1.93","doi-asserted-by":"crossref","first-page":"154","DOI":"10.1186\/s12944-024-02121-0","article-title":"Prognostic potential of lipid profiling in cancer patients: a systematic review of mass spectrometry-based studies","volume":"23","year":"2024","journal-title":"Lipids Health Dis"},{"key":"2026100808500827000_2026.10.01.756059v1.94","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000121568.40692.97"},{"key":"2026100808500827000_2026.10.01.756059v1.95","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3109\/09537104.2012.661107","article-title":"Inhibition of platelet aggregation by prostaglandin E1 (PGE1) in diabetic patients during therapy with clopidogrel and aspirin","volume":"24","year":"2013","journal-title":"Platelets"},{"key":"2026100808500827000_2026.10.01.756059v1.96","doi-asserted-by":"crossref","unstructured":"Z. Kov\u00e1cs et al., Critical Role of Astrocytic Polyamine and GABA Metabolism in Epileptogenesis. Frontiers in Cellular Neuroscience Volume 15 - 2021, (2022).","DOI":"10.3389\/fncel.2021.787319"},{"key":"2026100808500827000_2026.10.01.756059v1.97","doi-asserted-by":"crossref","first-page":"14498","DOI":"10.1002\/cam4.6102","article-title":"Insights into the leveraging of GABAergic signaling in cancer therapy","volume":"12","year":"2023","journal-title":"Cancer medicine"},{"key":"2026100808500827000_2026.10.01.756059v1.98","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2017.03.008"},{"key":"2026100808500827000_2026.10.01.756059v1.99","doi-asserted-by":"publisher","DOI":"10.2337\/db12-0466"},{"key":"2026100808500827000_2026.10.01.756059v1.100","doi-asserted-by":"publisher","DOI":"10.1007\/BF00391361"},{"key":"2026100808500827000_2026.10.01.756059v1.101","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-16-3062"},{"key":"2026100808500827000_2026.10.01.756059v1.102","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M004747"},{"key":"2026100808500827000_2026.10.01.756059v1.103","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1038\/s41467-025-56894-8","article-title":"Targeting ELOVL6 to disrupt c-MYC driven lipid metabolism in pancreatic cancer enhances chemosensitivity","volume":"16","year":"2025","journal-title":"Nature Communications"},{"key":"2026100808500827000_2026.10.01.756059v1.104","doi-asserted-by":"crossref","first-page":"2729","DOI":"10.1016\/j.celrep.2020.01.080","article-title":"Macropinocytosis Renders a Subset of Pancreatic Tumor Cells Resistant to mTOR Inhibition","volume":"30","year":"2020","journal-title":"Cell Reports"},{"key":"2026100808500827000_2026.10.01.756059v1.105","doi-asserted-by":"crossref","unstructured":"E. T. Pavlidis , I. N. Galanis , T. E. Pavlidis , Updates in the diagnosis and management of ductal adenocarcinoma of the pancreas. World Journal of Clinical Oncology 16, 105601 (2025).","DOI":"10.5306\/wjco.v16.i6.105601"},{"key":"2026100808500827000_2026.10.01.756059v1.106","doi-asserted-by":"crossref","unstructured":"D. R. Principe et al., The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy. Front Oncol 11, 688377 (2021).","DOI":"10.3389\/fonc.2021.688377"},{"key":"2026100808500827000_2026.10.01.756059v1.107","doi-asserted-by":"crossref","first-page":"4023","DOI":"10.1200\/JCO.2022.40.16_suppl.4023","article-title":"Phase 3, multicenter, randomized study of CPI-613 with modified FOLFIRINOX (mFFX) versus FOLFIRINOX (FFX) as first-line therapy for patients with metastatic adenocarcinoma of the pancreas (AVENGER500)","volume":"40","year":"2022","journal-title":"Journal of Clinical Oncology"},{"key":"2026100808500827000_2026.10.01.756059v1.108","doi-asserted-by":"publisher","DOI":"10.1093\/annonc\/mds135"},{"key":"2026100808500827000_2026.10.01.756059v1.109","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.21.01604"},{"key":"2026100808500827000_2026.10.01.756059v1.110","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2208470"},{"key":"2026100808500827000_2026.10.01.756059v1.111","doi-asserted-by":"publisher","DOI":"10.1200\/jco.23.00434"},{"key":"2026100808500827000_2026.10.01.756059v1.112","doi-asserted-by":"crossref","first-page":", 724","DOI":"10.1200\/JCO.2025.43.4_suppl.724","article-title":"Preliminary safety, antitumor activity, and circulating tumor DNA (ctDNA) changes with RMC-9805, an oral, RAS(ON) G12D-selective tri-complex inhibitor in patients with KRAS G12D pancreatic ductal adenocarcinoma (PDAC) from a phase 1 study in advanced solid tumors","volume":"43","year":"2025","journal-title":"Journal of Clinical Oncology"},{"key":"2026100808500827000_2026.10.01.756059v1.113","doi-asserted-by":"crossref","first-page":", S486","DOI":"10.1016\/j.annonc.2024.08.675","article-title":"608O Preliminary safety and clinical activity of ASP3082, a first-in-class, KRAS G12D selective protein degrader in adults with advanced pancreatic (PC), colorectal (CRC), and non-small cell lung cancer (NSCLC)","volume":"35","year":"2024","journal-title":"Annals of Oncology"},{"key":"2026100808500827000_2026.10.01.756059v1.114","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2025.43.4_suppl.722"},{"key":"2026100808500827000_2026.10.01.756059v1.115","doi-asserted-by":"crossref","unstructured":"M. Zhao et al., Macropinocytosis: Both a Target and a Tool for Cancer Therapy. Biomolecules 15, 936 (2025).","DOI":"10.3390\/biom15070936"},{"key":"2026100808500827000_2026.10.01.756059v1.116","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.012578299"},{"key":"2026100808500827000_2026.10.01.756059v1.117","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-04-082495"},{"key":"2026100808500827000_2026.10.01.756059v1.118","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2006.04.055"},{"key":"2026100808500827000_2026.10.01.756059v1.119","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gki376"},{"key":"2026100808500827000_2026.10.01.756059v1.120","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-19-0556"},{"key":"2026100808500827000_2026.10.01.756059v1.121","doi-asserted-by":"crossref","unstructured":"B. Gy\u0151rffy , Integrated analysis of public datasets for the discovery and validation of survival-associated genes in solid tumors. Innovation (Camb ) 5, 100625 (2024).","DOI":"10.1016\/j.xinn.2024.100625"},{"key":"2026100808500827000_2026.10.01.756059v1.122","doi-asserted-by":"crossref","unstructured":"S. Y\u0131lmaz et al., Making proteomics accessible: RokaiXplorer for interactive analysis of phospho-proteomic data. Bioinformatics Advances 4, (2024).","DOI":"10.7490\/f1000research.1120018.1"},{"key":"2026100808500827000_2026.10.01.756059v1.123","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkv468"},{"key":"2026100808500827000_2026.10.01.756059v1.124","doi-asserted-by":"crossref","unstructured":"S. B. Breitkopf et al., A relative quantitative positive\/negative ion switching method for untargeted lipidomics via high resolution LC-MS\/MS from any biological source. Metabolomics 13, (2017).","DOI":"10.1007\/s11306-016-1157-8"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.64898\/2026.10.01.756059","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T15:50:20Z","timestamp":1791474620000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.64898\/2026.10.01.756059"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,5]]},"references-count":124,"URL":"https:\/\/doi.org\/10.64898\/2026.10.01.756059","relation":{},"subject":[],"published":{"date-parts":[[2026,10,5]]},"subtype":"preprint"}}