Gray M E, Lee S, McDowell A L, Erskine M, Loh Q T M, Grice O, Argyle D J, Bergkvist G T
The Royal (Dick) School of Veterinary Studies and The Roslin Institute, The University of Edinburgh, Midlothian, EH25 9RG, UK.
Vet Comp Oncol. 2017 Sep;15(3):890-909. doi: 10.1111/vco.12230. Epub 2016 May 27.
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.
表皮生长因子受体（EGFR/ERBB）基因家族成员在一系列人类癌症中经常发生失调，针对这些蛋白的治疗方法正在临床应用中。我们假设类似的途径参与猫和狗的肿瘤，并且相同的药物可能对兽医患者有临床应用价值。我们使用一组猫和狗的细胞系研究了EGFR和ERBB2的靶向作用。用小干扰RNA（siRNA）或酪氨酸激酶抑制剂（TKI）靶向EGFR和ERBB2，并在体外研究它们对细胞增殖、集落形成和迁移的影响。在此我们报告，EGFR和ERBB2联合siRNA靶向在猫和狗的细胞系中产生了协同效应，类似于在人类细胞系中报道的情况。我们得出结论，使用TKI双重靶向EGFR和ERBB2作为猫头颈和乳腺肿瘤以及狗乳腺肿瘤的潜在新治疗策略应进一步评估。
