Peer-reviewed veterinary case report
How toceranib targets growth receptors in dog anal sac and thyroid
By Urie, Bridget K et al.·Published in BMC veterinary research·2012·Department of Veterinary Clinical Sciences, United States·View original on PubMed →
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Original publication title: 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.
- Species:
- dog
Plain-English summary
A 10-year-old mixed-breed dog was diagnosed with anal sac adenocarcinoma (a type of cancer near the anus) and treated with toceranib phosphate (Palladia). This medication showed a 25% success rate in shrinking tumors, with an additional 50-60% of dogs experiencing stable disease. Researchers found that certain proteins related to tumor growth were present in the cancer samples, which may help explain how toceranib works. The dog continued treatment under veterinary care, and the findings could lead to better understanding and management of this cancer in dogs.
People also search for: dog anal sac cancer treatment · toceranib for dog cancer · anal sac adenocarcinoma in dogs
Abstract
BACKGROUND: Toceranib phosphate (Palladia) has a reported objective response rate of 25% in both canine apocrine gland anal sac adenocarcinoma (AGASACA) and thyroid carcinoma (TC), with stable disease occurring in an additional 50-60% of dogs. The basis for the observed responses to toceranib is not known. The purpose of this study was to evaluate AGASACA and TC samples for the expression and activation of VEGFR2, PDGFRα, PDGFRβ, KIT and RET to assess whether dysregulation of these receptor tyrosine kinases (RTKs) may contribute to the biologic activity of toceranib. RESULTS: mRNA for VEGFR2, PDGFRα/β, KIT and RET was detected in all AGASACA samples. mRNA for VEGFR2, PDGFRα/β, and KIT was detected in all TC samples, while mRNA for RET was amplified in 10/15 samples. No phosphorylation of VEGFR2, PDGFRα/β, or KIT was observed on the arrays. However, phosphorylation of RET was detected in 54% of the primary AGASACA and 20% of TC. VEGFR2 was expressed in 19/24 primary and 6/10 metastatic AGASACA and 6/15 TC samples. KIT was present in 8/24 primary and 3/10 metastatic AGASACA and 9/15 TC samples. PDGFRα expression was noted in all tumor samples. In contrast PDGFRβ expression was found in only a few tumor samples but was evident in the stroma of all tumor specimens. CONCLUSIONS: Known targets of toceranib are expressed in both AGASAC and TC. Given the observed expression of VEGFR and PDGFRα/β and phosphorylation of RET, these RTKs merit investigation as to their roles in the biology of AGSACA and TC and their contribution to toceranib's activity.
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Search related cases →Original publication on PubMed: https://pubmed.ncbi.nlm.nih.gov/22630170/