Tyrosine kinase inhibitors in veterinary oncology

Tyrosine kinases are critical regulators of normal cell signalling, because they control several key processes. Tyrosine kinases are specific signalling molecules playing an essential role in cell growth, survival, migration and differentiation. Their receptors are located on the cell surface, delivering signals to the nucleus through a phosphorylation cascade. Receptor tyrosine kinases are those tyrosine kinases expressed on the cell surface that are stimulated by binding of growth factors. Tyrosine kinases are also of paramount importance in angiogenesis, and thus, in the development of tumor vascularisation. The emergence of abnormal signalling pathways due to the dysregulation of receptor tyrosine kinases is a known feature in several tumour types, and is regarded as a negative prognostic factor, as it alters tumor growth, proliferation and metastatic potential. Inhibition of tyrosine kinases is very important in human oncology, and it is likely that many more tyrosine kinase inhibitors will become available in the near future; and their biological activity will be enhanced as combination regimens with standard treatment modalities are explored. The use of kinase inhibitors in dogs and cats is relatively recent. There are now 2 small molecule inhibitors approved for use in veterinary medicine: Palladia (toceranib) and Masivet/Kinavet (masitinib). Their use is approved in mast cell tumours of dogs by the Federal Drug Administration (USA). Gleevec (imatinib) is human tyrosine kinase inhibitor used in the treatment of multiple human cancers (for example chronic myelogenous leukaemia and GIST), but has been successfully used in dogs and cats as well. The authors review the current knowledge on the biology of tyrosine kinase dysfunction in human and animal cancers, and the application of specific tyrosine kinase inhibitors to veterinary cancer patients.