Oncogenic Addiction to ERBB2 Signaling Predicts Response to Trastuzumab in Urothelial Cancer.

TitleOncogenic Addiction to ERBB2 Signaling Predicts Response to Trastuzumab in Urothelial Cancer.
Publication TypeJournal Article
Year of Publication2019
AuthorsKarass M, Bareja R, Shelkey E, Vlachostergios PJ, Robinson BD, Khani F, Mosquera JMiguel, Scherr DS, Sboner A, Tagawa ST, Molina AM, Elemento O, Nanus DM, Faltas BM
JournalJ Natl Compr Canc Netw
Date Published2019 03 01
KeywordsAged, Antineoplastic Agents, Immunological, Cell Line, Tumor, Female, Gene Expression Regulation, Neoplastic, Genotype, Humans, Immunohistochemistry, Neoplasm Staging, Oncogene Addiction, Receptor, ErbB-2, RNA, Messenger, Sequence Analysis, DNA, Signal Transduction, Tomography, X-Ray Computed, Trastuzumab, Urethral Neoplasms, Whole Exome Sequencing

Urothelial carcinoma (UC) is a common and frequently lethal cancer. Despite the presence of genomic alterations creating dependency on particular signaling pathways, the use of targeted therapies in advanced and metastatic UC has been limited. We performed an integrated analysis of whole-exome and RNA sequencing of primary and metastatic tumors in a patient with platinum-resistant UC. We found a strikingly high ERBB2 mRNA expression and enrichment of downstream oncogenic ERBB2 signaling in this patient's tumors compared with tumors from an unselected group of patients with UC (N=17). This patient had an exceptional sustained response to trastuzumab. Our findings show that oncogenic addiction to ERBB2 signaling potentially predicts response to ERBB2-directed therapy of UC.

Alternate JournalJ Natl Compr Canc Netw
PubMed ID30865916