Applied precision medicine in metastatic pancreatic ductal adenocarcinoma

Therapeutic Advances in Medical Oncology
Hossein TaghizadehGerald W Prager

Abstract

Metastatic pancreatic ductal adenocarcinoma (mPDAC) bears a dismal prognosis due to the limited activity of systemic chemotherapy. In our platform for precision medicine, we aim to offer molecular-guided treatments to patients without further standard therapy options. In this single center, real-world retrospective analysis of our platform, we describe the molecular-based therapy approaches used in all 50 patients diagnosed with therapy-refractory mPDAC. A molecular portrait of the tumor specimens was created by next-generation sequencing, immunohistochemistry (IHC), microsatellite instability (MSI) testing, and fluorescence in situ hybridization. In total, we detected 123 mutations in 50 patients. The five most frequent mutations were KRAS (n = 40; 80%), TP53 (n = 29; 58%), CDKN2A (n = 8; 16%), SMAD4 (n = 4; 8%), and NOTCH1 (n = 4; 8%), which together accounted for 40.2% of all mutations. Two patients had gene fusions, namely, TBL1XR1-PIK3CA and EIF3E-RSPO2. IHC detected expression of EGFR, phosphorylated mTOR, and PTEN in 36 (72%), 33 (66%), and 17 patients (34%), respectively. For 14 (28%) of the 50 patients, a targeted therapy was suggested based on the identified molecular targets. The recommended treatments included the m...Continue Reading

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Citations

Dec 4, 2020·International Journal of Molecular Sciences·Chiara BazzichettoMichele Milella
Jun 18, 2021·Advanced Drug Delivery Reviews·Alexandros Marios SofiasTwan Lammers

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Methods Mentioned

BETA
surgical resection
Assay
biopsy
imaging techniques

Software Mentioned

GLOBOCAN
TAPUR
SPSS Statistics
MSI Analysis System

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