Her2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy.

Kiss, Bernhard; Wyatt, Alexander W; Douglas, James; Skuginna, Veronika Olga; Mo, Fan; Anderson, Shawn; Rotzer, Diana; Fleischmann, Achim; Genitsch Gratwohl, Vera; Hayashi, Tetsutaro; Neuenschwander, Maja; Buerki, Christine; Davicioni, Elai; Collins, Colin; Thalmann, George; Black, Peter C; Seiler, Roland (2017). Her2 alterations in muscle-invasive bladder cancer: Patient selection beyond protein expression for targeted therapy. Scientific Reports, 7(42713), p. 42713. Nature Publishing Group 10.1038/srep42713

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Although the introduction of novel targeted agents has improved patient outcomes in several human cancers, no such advance has been achieved in muscle-invasive bladder cancer (MIBC). However, recent sequencing efforts have begun to dissect the complex genomic landscape of MIBC, revealing distinct molecular subtypes and offering hope for implementation of targeted therapies. Her2 (ERBB2) is one of the most established therapeutic targets in breast and gastric cancer but agents targeting Her2 have not yet demonstrated anti-tumor activity in MIBC. Through an integrated analysis of 127 patients from three centers, we identified alterations of Her2 at the DNA, RNA and protein level, and demonstrate that Her2 relevance as a tumor driver likely may vary even within ERBB2 amplified cases. Importantly, tumors with a luminal molecular subtype have a significantly higher rate of Her2 alterations than those of the basal subtype, suggesting that Her2 activity is also associated with subtype status. Although some of our findings present rare events in bladder cancer, our study suggests that comprehensively assessing Her2 status in the context of tumor molecular subtype may help select MIBC patients most likely to respond to Her2 targeted therapy.

Item Type:

Journal Article (Original Article)

Division/Institute:

04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Urology
04 Faculty of Medicine > Service Sector > Institute of Pathology > Clinical Pathology

UniBE Contributor:

Kiss, Bernhard; Skuginna, Veronika Olga; Genitsch Gratwohl, Vera; Thalmann, George and Seiler, Roland

Subjects:

600 Technology > 610 Medicine & health

ISSN:

2045-2322

Publisher:

Nature Publishing Group

Language:

English

Submitter:

Katharina Morgenegg

Date Deposited:

10 Jul 2017 09:38

Last Modified:

16 Jul 2017 02:14

Publisher DOI:

10.1038/srep42713

PubMed ID:

28205537

BORIS DOI:

10.7892/boris.96880

URI:

https://boris.unibe.ch/id/eprint/96880

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