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Bioinformatory-assisted analysis of next-generation sequencing data for precision medicine in pancreatic cancer
- Source :
- Molecular Oncology
- Publication Year :
- 2017
- Publisher :
- Wiley, 2017.
-
Abstract
- Pancreatic ductal adenocarcinoma (PDAC) is a tumor with an extremely poor prognosis, predominantly as a result of chemotherapy resistance and numerous somatic mutations. Consequently, PDAC is a prime candidate for the use of sequencing to identify causative mutations, facilitating subsequent administration of targeted therapy. In a feasibility study, we retrospectively assessed the therapeutic recommendations of a novel, evidence-based software that analyzes next-generation sequencing (NGS) data using a large panel of pharmacogenomic biomarkers for efficacy and toxicity. Tissue from 14 patients with PDAC was sequenced using NGS with a 620 gene panel. FASTQ files were fed into treatmentmap. The results were compared with chemotherapy in the patients, including all side effects. No changes in therapy were made. Known driver mutations for PDAC were confirmed (e.g. KRAS, TP53). Software analysis revealed positive biomarkers for predicted effective and ineffective treatments in all patients. At least one biomarker associated with increased toxicity could be detected in all patients. Patients had been receiving one of the currently approved chemotherapy agents. In two patients, toxicity could have been correctly predicted by the software analysis. The results suggest that NGS, in combination with an evidence-based software, could be conducted within a 2-week period, thus being feasible for clinical routine. Therapy recommendations were principally off-label use. Based on the predominant KRAS mutations, other drugs were predicted to be ineffective. The pharmacogenomic biomarkers indicative of increased toxicity could be retrospectively linked to reported negative side effects in the respective patients. Finally, the occurrence of somatic and germline mutations in cancer syndrome-associated genes is noteworthy, despite a high frequency of these particular variants in the background population. These results suggest software-analysis of NGS data provides evidence-based information on effective, ineffective and toxic drugs, potentially forming the basis for precision cancer medicine in PDAC.
- Subjects :
- 0301 basic medicine
Cancer Research
medicine.medical_treatment
pancreatic cancer
medicine.disease_cause
Bioinformatics
Targeted therapy
0302 clinical medicine
Prospective Studies
Precision Medicine
Research Articles
Aged, 80 and over
education.field_of_study
High-Throughput Nucleotide Sequencing
bioinformatics
evidence‐based
Genomics
General Medicine
Middle Aged
Oncology
NGS
030220 oncology & carcinogenesis
Molecular Medicine
KRAS
Research Article
Carcinoma, Pancreatic Ductal
Adult
Population
Antineoplastic Agents
Proto-Oncogene Proteins p21(ras)
03 medical and health sciences
Germline mutation
Pancreatic cancer
Genetics
medicine
Humans
education
Germ-Line Mutation
Aged
business.industry
Cancer
Precision medicine
medicine.disease
Pancreatic Neoplasms
030104 developmental biology
Pharmacogenomics
Mutation
drug–drug interactions
Feasibility Studies
Tumor Suppressor Protein p53
business
Software
Subjects
Details
- ISSN :
- 15747891
- Volume :
- 11
- Database :
- OpenAIRE
- Journal :
- Molecular Oncology
- Accession number :
- edsair.doi.dedup.....426db631a041830bf3f1024c6bac8e33