Krentel, Friedemann; Singer, Franziska; Rosano-Gonzalez, María Lourdes; Gibb, Ewan A; Liu, Yang; Davicioni, Elai; Keller, Nicola; Stekhoven, Daniel J; Kruithof-de Julio, Marianna; Seiler-Blarer, Roland (2021). A showcase study on personalized in silico drug response prediction based on the genetic landscape of muscle invasive bladder cancer. Scientific Reports, 11(1), p. 5849. Nature Publishing Group 10.1038/s41598-021-85151-3
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Improved and cheaper molecular diagnostics allow the shift from "one size fits all" therapies to personalised treatments targeting the individual tumor. However, the wealth of potential targets based on comprehensive sequencing remains a yet unsolved challenge that prevents its routine use in clinical practice. Thus, we designed a workflow that selects the most promising treatment targets based on multi-omics sequencing and in silico drug prediction. In this study we demonstrate the workflow with focus on bladder cancer (BLCA), as there are, to date, no reliable diagnostics available to predict the potential benefit of a therapeutic approach. Within the TCGA-BLCA cohort, our workflow identified a panel of 21 genes and 72 drugs that suggested personalized treatment for 95% of patients-including five genes not yet reported as prognostic markers for clinical testing in BLCA. The automated predictions were complemented by manually curated data, thus allowing for accurate sensitivity- or resistance-directed drug response predictions. We discuss potential improvements of drug-gene interaction databases on the basis of pitfalls that were identified during manual curation.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > DBMR Forschung Mu35 > Forschungsgruppe Urologie 04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology |
UniBE Contributor: |
Krentel, Andreas Friedemann, Kruithof-de Julio, Marianna, Seiler-Blarer, Roland |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2045-2322 |
Publisher: |
Nature Publishing Group |
Language: |
English |
Submitter: |
Jeannine Wiemann |
Date Deposited: |
13 Oct 2021 11:01 |
Last Modified: |
05 Dec 2022 15:53 |
Publisher DOI: |
10.1038/s41598-021-85151-3 |
PubMed ID: |
33712636 |
BORIS DOI: |
10.48350/159670 |
URI: |
https://boris.unibe.ch/id/eprint/159670 |