Related Experiment Video
Updated: Jul 31, 2025
Testing Targeted Therapies in Cancer using Structural DNA Alteration Analysis and Patient-Derived Xenografts
Published on: July 25, 2020
Smaller panel, similar results: genomic profiling and molecularly informed therapy in pancreatic cancer
T M Reissig1, I Tzianopoulos2, S-T Liffers3
1Bridge Institute of Experimental Tumor Therapy, West German Cancer Center, University Hospital Essen, Essen, Germany; Division of Solid Tumor Translational Oncology, German Cancer Research Center (DKFZ) and German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Heidelberg, Germany; Department of Medical Oncology, West German Cancer Center, University Hospital Essen, Essen, Germany; German Cancer Consortium (DKTK), Partner Site University Hospital Essen, Essen, Germany.
Background:
Pancreatic cancer has a dismal prognosis. One reason is resistance to cytotoxic drugs. Molecularly matched therapies might overcome this resistance but the best approach to identify those patients who may benefit is unknown. Therefore, we sought to evaluate a molecularly guided treatment approach.
Materials And Methods:
We retrospectively analyzed the clinical outcome and mutational status of patients with pancreatic cancer who received molecular profiling at the West German Cancer Center Essen from 2016 to 2021. We carried out a 47-gene DNA next-generation sequencing (NGS) panel. Furthermore, we assessed microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) status and, sequentially and only in case of KRAS wild-type, gene fusions via RNA-based NGS. Patient data and treatment were retrieved from the electronic medical records.
Results:
Of 190 included patients, 171 had pancreatic ductal adenocarcinoma (90%). One hundred and three patients had stage IV pancreatic cancer at diagnosis (54%). MMR analysis in 94 patients (94/190, 49.5%) identified 3 patients with dMMR (3/94, 3.2%). Notably, we identified 32 patients with KRAS wild-type status (16.8%). To identify driver alterations in these patients, we conducted an RNA-based fusion assay on 13 assessable samples and identified 5 potentially actionable fusions (5/13, 38.5%). Overall, we identified 34 patients with potentially actionable alterations (34/190, 17.9%). Of these 34 patients, 10 patients (10/34, 29.4%) finally received at least one molecularly targeted treatment and 4 patients had an exceptional response (>9 months on treatment).
Conclusions:
Here, we show that a small-sized gene panel can suffice to identify relevant therapeutic options for pancreatic cancer patients. Informally comparing with previous large-scale studies, this approach yields a similar detection rate of actionable targets. We propose molecular sequencing of pancreatic cancer as standard of care to identify KRAS wild-type and rare molecular subsets for targeted treatment strategies.
Insights
Molecular profiling identifies actionable targets in pancreatic cancer, including KRAS wild-type and rare subsets. A small gene panel approach can guide targeted treatments, improving outcomes for patients with this dismal prognosis disease.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Pancreatic cancer exhibits poor prognosis, largely due to resistance to conventional chemotherapy.
- Identifying patients who can benefit from molecularly matched therapies is crucial for improving treatment outcomes.
- A molecularly guided treatment approach may overcome drug resistance in pancreatic cancer.
Purpose of the Study:
- To evaluate the efficacy of a molecularly guided treatment approach for pancreatic cancer patients.
- To assess the utility of a targeted gene panel for identifying actionable alterations.
- To determine the feasibility of identifying KRAS wild-type and other rare molecular subsets for targeted therapies.
Main Methods:
- Retrospective analysis of clinical outcomes and mutational status in 190 pancreatic cancer patients.
- Utilized a 47-gene DNA next-generation sequencing (NGS) panel for molecular profiling.
- Assessed microsatellite instability-high/deficient mismatch repair (MSI-H/dMMR) and RNA-based gene fusions in KRAS wild-type cases.
Main Results:
- Identified potentially actionable alterations in 17.9% (34/190) of patients.
- KRAS wild-type status was observed in 16.8% (32/190) of patients.
- Of the 34 patients with actionable alterations, 10 received targeted treatment, with 4 experiencing exceptional responses (>9 months).
Conclusions:
- A targeted gene panel is effective in identifying therapeutic options for pancreatic cancer.
- This molecular profiling approach can detect actionable targets at rates comparable to larger studies.
- Recommends molecular sequencing as standard of care to identify KRAS wild-type and rare subsets for targeted treatment strategies.
Related Concept Videos
02:50Combination Therapies and Personalized Medicine
The combination of the drug acetazolamide and sulforaphane is a good example of combination therapy to treat cancer. The cells in the interior of a large tumor often die due to the hypoxic and...
02:57Targeted Cancer Therapies
There are several types of targeted therapies against...