Urachal Carcinoma Shares Genomic Alterations with Colorectal Carcinoma and May Respond to Epidermal Growth Factor Inhibition. Academic Article uri icon

Overview

abstract

  • UNLABELLED: Metastatic urachal carcinoma is a rare, understudied, and aggressive malignancy with limited treatment options. Histologically, urachal carcinomas resemble enteric adenocarcinomas and anecdotally respond to systemic therapies utilized in colorectal cancer. Targeted exome sequencing of archival primary tumor tissue from a patient with metastatic urachal cancer revealed EGFR amplification and wild-type KRAS. The patient was treated with cetuximab, a monoclonal antibody directed against EGFR, as a single agent, and achieved a response lasting more than 8 mo. Subsequent whole-exome sequencing revealed no additional alterations likely to be associated with cetuximab sensitivity. Formalin-fixed, paraffin-embedded tumor specimens from nine additional urachal cancers were subjected to targeted exome sequencing. Mitogen-activated protein kinase (MAPK) pathway mutations were found in four of the nine samples, but no EGFR amplification was detected. Importantly, APC mutations were detected in two of the nine patients. To our knowledge, this is the first report of a response to single-agent cetuximab in a patient with metastatic urachal cancer and of molecular analysis to probe the basis for sensitivity. On the basis of these findings and the histologic, and now genomic, similarities with colorectal cancer, monoclonal antibodies directed at EGFR could be used in the treatment of metastatic urachal cancer. PATIENT SUMMARY: Urachal cancers are morphologically and genomically similar to colon adenocarcinomas and may respond to drugs targeting the epidermal growth factor receptor.

publication date

  • May 10, 2016

Research

keywords

  • Adenocarcinoma
  • Cetuximab
  • Colonic Neoplasms
  • Drug Resistance, Neoplasm
  • ErbB Receptors
  • Proto-Oncogene Proteins p21(ras)
  • Urinary Bladder Neoplasms

Identity

PubMed Central ID

  • PMC5489411

Scopus Document Identifier

  • 84975165540

Digital Object Identifier (DOI)

  • 10.18632/oncotarget.8076

PubMed ID

  • 27178450

Additional Document Info

volume

  • 70

issue

  • 5