{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,19]],"date-time":"2026-03-19T10:33:05Z","timestamp":1773916385980,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T00:00:00Z","timestamp":1773705600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["5P20GM121288-07"],"award-info":[{"award-number":["5P20GM121288-07"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["CA234324"],"award-info":[{"award-number":["CA234324"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100000043","name":"American Association for Cancer Research","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100000043","id-type":"DOI","asserted-by":"crossref"}]},{"name":"NIH","award":["DP2CA301099"],"award-info":[{"award-number":["DP2CA301099"]}]},{"name":"NCI\u2014Cancer Center Support Grant","award":["P30CA134274"],"award-info":[{"award-number":["P30CA134274"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Pancreatic ductal adenocarcinoma (PDAC) is an aggressive malignancy with a 5-year survival rate of 13.3%. First-line treatment relies on two chemotherapy regimens, FOLFIRINOX (FOLFNX) or gemcitabine plus nab-paclitaxel (GEMPAC). However, direct clinical comparisons between these regimens have yielded inconsistent results across survival and toxicity endpoints, and the molecular basis of heterogeneous treatment responses remains poorly defined. To investigate regimen-specific tumor-cell-intrinsic mechanisms, we performed quantitative proteomic profiling of a primary PDAC-derived MIA PaCa-2 cell line following treatment with FOLFNX or GEMPAC. Differentially expressed proteins were analyzed using Gene Ontology, KEGG, and Ingenuity Pathway Analysis to define pathway-level alterations, and findings were contextualized using TCGA transcriptomic data. Proteomic analyses revealed that FOLFNX and GEMPAC engage in distinct cytotoxic programs. FOLFNX predominantly suppressed ribosome biogenesis and mitochondrial translation, consistent with sustained metabolic and biosynthetic stress, whereas GEMPAC preferentially disrupted mitotic cytokinesis and phosphatidylinositol phosphate biosynthesis, consistent with mitotic failure. Integration with TCGA data showed that FOLFNX-altered proteins aligned with favorable prognostic expression signatures, whereas GEMPAC-associated proteins were enriched among adverse profiles, reflecting engagement of distinct tumor-intrinsic programs. Together, these findings provide mechanistic insight into differential chemotherapy responses and establish a foundation for proteomics-based biomarkers to guide personalized chemotherapy selection in PDAC.<\/jats:p>","DOI":"10.3390\/cells15060531","type":"journal-article","created":{"date-parts":[[2026,3,17]],"date-time":"2026-03-17T09:35:57Z","timestamp":1773740157000},"page":"531","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Comparative Proteomic Profiling of Responses to Standard Systemic Treatment Regimens in Pancreatic Cancer"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9014-5024","authenticated-orcid":false,"given":"Amirsalar","family":"Mansouri","sequence":"first","affiliation":[{"name":"Department of Interdisciplinary Oncology, Louisiana State University (LSU) Health School of Medicine-New Orleans, New Orleans, LA 70112, USA"},{"name":"LSU-LCMC Health Cancer 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65211, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7702-4308","authenticated-orcid":false,"given":"Aleksandra","family":"Cios","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"Department of Pharmacology and Physiology, University of Maryland, Baltimore, MD 20740, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zetao","family":"Cheng","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum NCI Comprehensive Cancer Center, School of Medicine, University of Maryland, Baltimore, MD 21201, USA"},{"name":"Department of Pharmacology and Physiology, University of Maryland, Baltimore, MD 20740, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6226-9062","authenticated-orcid":false,"given":"Sudhakar","family":"Ammanamanchi","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, Louisiana State University (LSU) Health School of Medicine-New Orleans, New Orleans, LA 70112, USA"},{"name":"LSU-LCMC Health Cancer Center, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5961-6761","authenticated-orcid":false,"given":"Jovanny","family":"Zabaleta","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, Louisiana State University (LSU) Health School of Medicine-New Orleans, New Orleans, LA 70112, USA"},{"name":"LSU-LCMC Health Cancer Center, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"suffix":"IV","given":"John H.","family":"Stewart","sequence":"additional","affiliation":[{"name":"Department of Surgery, Morehouse School of Medicine, Atlanta, GA 30310, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John T.","family":"West","sequence":"additional","affiliation":[{"name":"Department of Interdisciplinary Oncology, Louisiana State University (LSU) Health School of Medicine-New Orleans, New Orleans, LA 70112, USA"},{"name":"LSU-LCMC Health Cancer Center, New Orleans, LA 70112, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mitesh J.","family":"Borad","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology, Department of Internal Medicine, Mayo Clinic, Phoenix, AZ 85259, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2173-7912","authenticated-orcid":false,"given":"Bolni Marius","family":"Nagalo","sequence":"additional","affiliation":[{"name":"Marlene and Stewart Greenebaum NCI 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