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Dual targeting of EGFR and ERBB2 pathways produces a synergistic effect on cancer cell proliferation and migration in vitro

Vet Comp Oncol. 2017 Sep;15(3):890-909. doi: 10.1111/vco.12230. Epub 2016 May 27.

Abstract

Members of the epidermal growth factor receptor (EGFR/ERBB) gene family are frequently dysregulated in a range of human cancers, and therapeutics targeting these proteins are in clinical use. We hypothesized that similar pathways are involved in feline and canine tumours and that the same drugs may be of clinical use in veterinary patients. We investigated EGFR and ERBB2 targeting using a panel of feline and canine cell lines. EGFR and ERBB2 were targeted with siRNAs or tyrosine kinase inhibitors (TKIs) and their effect on cellular proliferation, colony formation and migration was investigated in vitro. Here we report that EGFR and ERBB2 combined siRNA targeting produced synergistic effects in feline and canine cell lines similar to that reported in human cell lines. We conclude that dual EGFR and ERBB2 targeting using TKIs should be further evaluated as a potential new therapeutic strategy in feline head and neck and mammary tumours and canine mammary tumours.

Keywords: cell signalling; comparative oncology; gene therapy; in vitro models; small animal; tumour biology; tyrosine kinase.

MeSH terms

  • Animals
  • Antineoplastic Agents / therapeutic use
  • Cat Diseases / drug therapy
  • Cat Diseases / metabolism
  • Cat Diseases / pathology
  • Cats
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / physiology
  • Cell Proliferation / drug effects
  • Cell Proliferation / physiology
  • Dog Diseases / drug therapy
  • Dog Diseases / metabolism
  • Dog Diseases / pathology
  • Dogs
  • Drug Synergism
  • ErbB Receptors / drug effects*
  • ErbB Receptors / genetics
  • ErbB Receptors / physiology
  • In Vitro Techniques
  • Neoplasms / drug therapy
  • Neoplasms / metabolism
  • Neoplasms / pathology
  • Neoplasms / veterinary*
  • Protein-Tyrosine Kinases / antagonists & inhibitors
  • RNA, Small Interfering / therapeutic use
  • Real-Time Polymerase Chain Reaction
  • Receptor, ErbB-2 / drug effects*
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / physiology
  • Signal Transduction / drug effects*
  • Signal Transduction / physiology

Substances

  • Antineoplastic Agents
  • RNA, Small Interfering
  • ErbB Receptors
  • Protein-Tyrosine Kinases
  • Receptor, ErbB-2