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Published on: September 8, 2023
Using next-generation sequencing to determine potential molecularly guided therapy options for patients with
Gerald Paul Wright1, David W Chesla2, Mathew H Chung3
1General Surgery Residency Program, Grand Rapids Medical Education Partners/Michigan State University General Surgery Residency Program, 221 Michigan St, Suite 200A, Grand Rapids, 49503, MI, USA; Department of Surgery, Michigan State University College of Human Medicine, 221 Michigan St, Suite 200A, Grand Rapids, MI, 49503, USA.
Background:
Genomic sequencing technology may identify personalized treatment options for patients with pancreatic adenocarcinoma.
Methods:
The study was conducted using tissue specimens obtained from 2012 to 2014. Patients with resected pancreatic adenocarcinoma were identified. Next-generation sequencing was performed from paraffin-tumor blocks. Mutational profiles were reviewed to determine available targeted therapies and clinical trial eligibility.
Results:
Thirty patients were identified. The incidence of mutations was: Kirsten rat sarcoma viral oncogene homolong (KRAS) = 87%, tumor protein 53 (TP53) = 63%, cyclin-dependent kinase inhibitor 2A (CDKN2A) = 20%, Mothers Against Decapentaplegic Homolog 4 (SMAD4) = 20%, epidermal growth factor receptor (EGFR) = 7%. Multiple mutations were found in 73%. All CDKN2A mutations occurred in male patients (P = .06), and there was a trend toward younger patient age in this group (P = .13). Potential for Federal Drug Administration (FDA)-approved targeted therapies was identified in 8 of 30 (27%). In addition, 29 of 30 (97%) had mutations applicable for ongoing phase I or II clinical trials.
Conclusions:
Next-generation sequencing of resected pancreatic adenocarcinoma specimens can determine common genetic mutations and identify patients who may be eligible for off-label use of targeted therapies or clinical trial enrollment.
Insights
Genomic sequencing of pancreatic cancer reveals common mutations like KRAS and TP53. This identifies patients eligible for targeted therapies and clinical trials, advancing personalized pancreatic adenocarcinoma treatment.
Area of Science:
- Oncology
- Genomics
- Personalized Medicine
Background:
- Pancreatic adenocarcinoma presents challenges in treatment selection.
- Genomic sequencing offers a pathway to identify personalized therapeutic strategies.
Purpose of the Study:
- To evaluate the utility of next-generation sequencing (NGS) in identifying actionable mutations in pancreatic adenocarcinoma.
- To determine patient eligibility for targeted therapies and clinical trials based on mutational profiles.
Main Methods:
- Retrospective analysis of tissue specimens from patients with resected pancreatic adenocarcinoma (2012-2014).
- Next-generation sequencing (NGS) performed on paraffin-embedded tumor blocks.
- Review of mutational profiles to assess targeted therapy and clinical trial eligibility.
Main Results:
- Eighty-seven percent of patients had Kirsten rat sarcoma viral oncogene homolog (KRAS) mutations; 63% had tumor protein 53 (TP53) mutations.
- Multiple mutations were identified in 73% of cases.
- Twenty-seven percent of patients were eligible for FDA-approved targeted therapies, and 97% were eligible for clinical trials.
Conclusions:
- NGS of pancreatic adenocarcinoma specimens effectively identifies common genetic mutations.
- This approach can guide patient selection for targeted therapies and clinical trial enrollment.
- Genomic profiling is crucial for advancing personalized treatment strategies in pancreatic cancer.
