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Updated: Dec 17, 2025
An Orthotopic Resectional Mouse Model of Pancreatic Cancer
Published on: September 24, 2020
A step towards personalizing next line therapy for resected pancreatic and related cancer patients: A single
Cinthya Y Lowder1, Teena Dhir2, Austin B Goetz1
1Department of Surgery, Albert Einstein Medical Center, Philadelphia, PA, USA.
Background:
There is a lack of precision medicine in pancreatic ductal adenocarcinoma (PDA) and related cancers, and outcomes for patients with this diagnosis remain poor despite decades of research investigating this disease. Therefore, it is necessary to explore novel therapeutic options for these patients who may benefit from personalized therapies.
Objective:
Molecular profiling of hepatopancreaticobiliary malignancies at our institution, including but not limited to PDA, was initiated to assess the feasibility of incorporating molecular profiling results into patient oncological therapy planning.
Methods:
All eligible patients from Thomas Jefferson University (TJU) with hepatopancreaticobiliary tumors including PDA, who agreed to molecular testing profiling, were prospectively enrolled in a registry study from December 2014 to September 2017 and their tumor samples were tested to identify molecular markers that can be used to guide therapy options in the future. Next generation sequencing (NGS) and protein expression in tumor samples were tested at CLIA-certified laboratories. Prospective clinicopathologic data were extracted from medical records and compiled in a de-identified fashion.
Results:
Seventy eight (78) patients were enrolled in the study, which included 65/78 patients with PDA (local and metastatic) and out of that subset, 52/65 patients had surgically resected PDA. Therapy recommendations were generated based on molecular and clinicopathologic data for all enrolled patients. NGS uncovered actionable alterations in 25/52 surgically resected PDAs (48%) which could be used to guide therapy options in the future. High expression of three proteins, TS (p = 0.005), ERCC1 (p = 0.001), and PD-1 (p = 0.04), was associated with reduced recurrence-free survival (RFS), while TP53 mutations were correlated with longer RFS (p = 0.01).
Conclusions:
The goal of this study was to implement a stepwise strategy to identify and profile resected PDAs at our institution. Consistent with previous studies, approximately half of patients with resected PDA harbor actionable mutations with possible targeted therapeutic implications. Ongoing studies will determine the clinical value of identifying these mutations in patients with resected PDA.
Insights
Molecular profiling of pancreatic ductal adenocarcinoma (PDA) identified actionable mutations in approximately half of resected tumors. This precision medicine approach may guide future targeted therapies for PDA patients, improving outcomes.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Pancreatic ductal adenocarcinoma (PDA) and related cancers lack precision medicine approaches, leading to poor patient outcomes.
- Novel therapeutic strategies are crucial for patients with PDA who could benefit from personalized therapies.
Purpose of the Study:
- To assess the feasibility of integrating molecular profiling into oncological therapy planning for hepatopancreaticobiliary malignancies.
- To identify molecular markers in PDA tumors to guide future treatment decisions.
Main Methods:
- Prospective enrollment of patients with hepatopancreaticobiliary tumors, including PDA, from December 2014 to September 2017.
- Tumor samples underwent next-generation sequencing (NGS) and protein expression analysis at CLIA-certified laboratories.
- Clinicopathologic data were collected and de-identified from medical records.
Main Results:
- Seventy-eight patients were enrolled, with 65 diagnosed with PDA; 52 had surgically resected PDA.
- NGS revealed actionable alterations in 48% (25/52) of surgically resected PDA samples.
- High expression of TS, ERCC1, and PD-1 correlated with reduced recurrence-free survival, while TP53 mutations were linked to longer recurrence-free survival.
Conclusions:
- A strategy was implemented to identify and profile resected PDAs.
- Approximately half of resected PDA patients have actionable mutations with potential therapeutic implications.
- Further studies are needed to determine the clinical utility of these molecular findings in resected PDA.
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