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Profiling Sensitivity to Targeted Therapies in EGFR-Mutant NSCLC Patient-Derived Organoids
Published on: November 22, 2021
EGFR amplification induces sensitivity to antiEGFR therapy in pancreatic acinar cell carcinoma
Corentin Richard1, Julie Niogret2, Romain Boidot1
1Platform of Transfer in Oncology, Center GF Leclerc, Dijon 21000, France.
Abstract:
Pancreatic acinar cell carcinoma (PACC) is a rare cancer. When the tumor is metastatic, few therapeutic options are available. Precision medicine using next-generation sequencing is defined by the administration of drugs based on the tumor genetic mutations. The usage of precision medicine for finding new therapeutic options for rare cancers is an emerging field. We have reported here the case of a patient bearing a multitreated metastatic PACC. This patient underwent somatic and constitutional exome analyses. The analyses revealed in the liver metastasis an amplification of the EGFR gene. Accordingly, the patient was treated with off-label usage of panitumumab. We observed rapid response with necrosis of the liver metastasis, while no efficacy was observed in the primary tumor. An exome analysis of the primary tumor revealed amplification of HER2 and MET with EGFR amplification. Such amplifications are known as a resistance mechanism to antiEGFR therapy. Our results suggest that exome analysis may be helpful to highlight targets in rare cancers, such as PACC. EGFR amplification in this pathology should be determined and could be used as a biomarker to propose antiEGFR therapy.
Insights
Precision medicine using next-generation sequencing identified an EGFR gene amplification in a metastatic pancreatic acinar cell carcinoma (PACC) patient. This led to successful targeted therapy, highlighting exome analysis for rare cancer treatment strategies.
Area of Science:
- Oncology
- Genomics
- Precision Medicine
Background:
- Pancreatic acinar cell carcinoma (PACC) is a rare malignancy with limited therapeutic options for metastatic disease.
- Precision medicine, guided by next-generation sequencing (NGS), offers a promising avenue for identifying novel treatments based on tumor-specific genetic mutations.
Observation:
- A patient with multi-treated metastatic PACC underwent comprehensive exome analysis.
- Liver metastasis revealed an amplification of the Epidermal Growth Factor Receptor (EGFR) gene.
Findings:
- Off-label treatment with panitumumab, an anti-EGFR therapy, resulted in rapid necrosis of the liver metastasis.
- Subsequent exome analysis of the primary tumor identified amplifications in HER2 and MET, alongside EGFR, suggesting potential resistance mechanisms to anti-EGFR therapy.
Implications:
- Exome sequencing can effectively identify actionable targets in rare cancers like PACC.
- EGFR amplification may serve as a valuable biomarker for guiding anti-EGFR therapy in PACC patients.
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