Comparative Proteomic Profiling of Responses to Standard Systemic Treatment Regimens in Pancreatic Cancer

Authors

• Amirsalar Mansouri, LSU Health Sciences Center - New OrleansFollow
• Olivia Hart, LSU Health Sciences Center - New OrleansFollow
• Sina Aslanabadi, LSU Health Sciences Center - New OrleansFollow
• Conner Hartupee, LSU Health Sciences Center - New OrleansFollow
• Dicle Yalcin, LSU Health Sciences Center - New OrleansFollow
• Garima Sinha, LSU Health Sciences Center - New OrleansFollow
• Chiswili Yves Chabu, University of Missouri, Columbia, MO
• Aleksandra Cios, University of Maryland, Baltimore, MD
• Zetao Cheng, University of Maryland, Baltimore, MD
• Sudhakar Ammanamanchi, LSU Health Sciences Center - New OrleansFollow
• Jovanny Zabaleta, LSU Health Sciences Center - New OrleansFollow
• John H. Stewart, Morehouse School of Medicine, Atlanta, GA
• John T. West, LSU Health Sciences Center - New OrleansFollow
• Mitesh J. Borad, Mayo Clinic, Phoenix, AZ
• Bolni Marius Nagalo, University of Maryland, Baltimore, MD
• Jiri Adamec, LSU Health Sciences Center - New OrleansFollow
• Omeed Moaven, LSU Health Sciences Center - New OrleansFollow

Document Type

Article

Publication Date

3-17-2026

Publication Title

Cells

Abstract

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.

First Page

1

Last Page

21

PubMed ID

41892321

Volume

15

Issue

6

Comments

Featured in Faculty Publications Display; May 2026

Creative Commons License

This work is licensed under a Creative Commons Attribution 4.0 International License.

Recommended Citation

Mansouri, Amirsalar; Hart, Olivia; Aslanabadi, Sina; Hartupee, Conner; Yalcin, Dicle; Sinha, Garima; Chabu, Chiswili Yves; Cios, Aleksandra; Cheng, Zetao; Ammanamanchi, Sudhakar; Zabaleta, Jovanny; Stewart, John H.; West, John T.; Borad, Mitesh J.; Nagalo, Bolni Marius; Adamec, Jiri; and Moaven, Omeed, "Comparative Proteomic Profiling of Responses to Standard Systemic Treatment Regimens in Pancreatic Cancer" (2026). School of Medicine Faculty Publications. 4654.
https://digitalscholar.lsuhsc.edu/som_facpubs/4654
10.3390/cells15060531