Quantitative proteomic analysis of HER2 protein expression in PDAC tumors

Jamie Randall, Allison L. Hunt, Aratara Nutcharoen, Laura Johnston, Safae Chouraichi, Hongkun Wang, Arthur Winer, Raymond Wadlow, Jasmine Huynh, Justin Davis, Brian Corgiat, Nicholas W. Bateman, John F. Deeken, Emanuel F. Petricoin, Thomas P. Conrads, Timothy L. Cannon*

*Corresponding author for this work

Research output: Contribution to journalLetterpeer-review

1 Scopus citations

Abstract

Metastatic pancreatic adenocarcinoma (PDAC) is the third leading cause of cancer-related death in the United States, with a 5-year survival rate of only 11%, necessitating identification of novel treatment paradigms. Tumor tissue specimens from patients with PDAC, breast cancer, and other solid tumor malignancies were collected and tumor cells were enriched using laser microdissection (LMD). Reverse phase protein array (RPPA) analysis was performed on enriched tumor cell lysates to quantify a 32-protein/phosphoprotein biomarker panel comprising known anticancer drug targets and/or cancer-related total and phosphorylated proteins, including HER2Total, HER2Y1248, and HER3Y1289. RPPA analysis revealed significant levels of HER2Total in PDAC patients at abundances comparable to HER2-positive (IHC 3+) and HER2-low (IHC 1+ /2+, FISH−) breast cancer tissues, for which HER2 screening is routinely performed. These data support a critical unmet need for routine clinical evaluation of HER2 expression in PDAC patients and examination of the utility of HER2-directed antibody–drug conjugates in these patients.

Original languageEnglish
Article number24
JournalClinical Proteomics
Volume21
Issue number1
DOIs
StatePublished - Dec 2024

Keywords

  • HER2
  • Laser microdissection
  • Pancreatic adenocarcinoma
  • Proteomics

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