Epidermal growth factor receptor as a therapeutic target in veterinary oncology

Abstract

Epidermal growth factor receptor (EGFR) is a tyrosine kinase receptor that stimulates cell proliferation and survival and becomes dysregulated in a range of solid tumours in man. It is recognized as a key oncogenic driver and has become a favoured therapeutic target and a prognostic and predictive marker of cancer in man. In animals, EGFR dysregulation is emerging as a potential factor in the development of a number of naturally occurring tumours including mammary, lung, glial and epithelial cancers. Comparative analyses suggest that these diseases share many features with equivalent diseases in man and EGFR may have value as a prognostic or a biological marker of animal disease. There is still little direct evidence that EGFR is a critical oncogenic driver in naturally occurring animal disease and there are no veterinary trials of EGFR-targeted therapy. These will be critical steps in establishing a role for EGFR in veterinary oncology.

Evaluation of expression and function of vascular endothelial growth factor receptor 2, platelet derived growth factor receptors-alpha and -beta, KIT, and RET in canine apocrine gland anal sac adenocarcinoma and thyroid carcinoma

“…While expression of EGFR has been evaluated in canine mammary tumors, brain tumors, nasal carcinomas, and lung tumors, it has yet to be proven as a driver of tumor proliferation in any canine cancer [45]. A recent report evaluating several markers in human thyroid carcinoma found strong EGFR expression in invasive PTC and FTC [46].…”

Gastric carcinoma associated with Menetrier's‐like disease in a West Highland white terrier

“…Treatment of Ménétrier's disease (Settle and others ) is based on a blocking monoclonal antibody directed towards the ectodomain of RTKs, associated with tyrosine kinase inhibitors in patients with gastric tumours. In dogs, RTKs are an interesting target and their involvement in many types of cancer is currently under the scope of many research programs, but so far there are few studies focussing on gastric tumours (Bergkvist and Yool , Doster and others , Singer and others ). Despite good results, there are still a lot of questions regarding the aetiology of Ménétrier's disease and its premalignant character.…”

Studies on the inhibition of feline EGFR in squamous cell carcinoma: Enhancement of radiosensitivity and rescue of resistance to small molecule inhibitors

“…If used in veterinary species they are likely to cause anti-human antibody responses similar to the human antimouse antibody responses seen in man to murine antibodies. 29,30 In this study gefitinib effectively reduced cellular migration and proliferation in the feline SCC cell line, but at the relatively typically transient in nature, with observed effects lasting up to one week. 24 To investigate if longer term knockdown of the receptor could be achieved, the siRNA sequence was cloned into a hairpin expression vector.…”