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

J Natl Compr Canc Netw. 2019 Mar 1;17(3):194-200. doi: 10.6004/jnccn.2018.7264.

Abstract

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.

Publication types

  • Case Reports
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Antineoplastic Agents, Immunological / pharmacology*
  • Cell Line, Tumor
  • Exome Sequencing
  • Female
  • Gene Expression Regulation, Neoplastic
  • Genotype
  • Humans
  • Immunohistochemistry
  • Neoplasm Staging
  • Oncogene Addiction* / genetics
  • RNA, Messenger / genetics
  • Receptor, ErbB-2 / antagonists & inhibitors
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Sequence Analysis, DNA
  • Signal Transduction / drug effects*
  • Tomography, X-Ray Computed
  • Trastuzumab / pharmacology*
  • Urethral Neoplasms / diagnosis*
  • Urethral Neoplasms / drug therapy
  • Urethral Neoplasms / etiology
  • Urethral Neoplasms / metabolism*

Substances

  • Antineoplastic Agents, Immunological
  • RNA, Messenger
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Trastuzumab