A showcase study on personalized in silico drug response prediction based on the genetic landscape of muscle invasive bladder cancer.

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)

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 and 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:

13 Oct 2021 11:01

Publisher DOI:

10.1038/s41598-021-85151-3

PubMed ID:

33712636

BORIS DOI:

10.48350/159670

URI:

https://boris.unibe.ch/id/eprint/159670

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