Tumor characteristics of feline injection-site sarcomas (ISS) can result in aggressive cellular infiltration, rapid proliferation, and ulcerative chronic inflammation. The overall prognosis for long-term control, even after surgery and radiation therapy, is poor, with most tumors recurring within 1–2 years. Studies have indicated that tyrosine kinase inhibitors (eg, masitinib) may have potential in ISS therapy because of disruption to the protein kinase cell signal pathway that regulates ISS cell growth, differentiation, and survival. Masitinib selectively targets platelet-derived growth factor receptor (PDGFR), as well as the stem cell receptor (c-kit), fibroblast growth factor receptor, and focal adhesion pathway. This study investigated the effects of masitinib on platelet-derived growth factor (PDGF) and PDGFR signaling, cell growth, and apoptosis in vitro.
The in vitro effects of masitinib were assessed in 2 feline ISS cell lines, one from a primary tumor and the second from a metastatic tumor in the same patient. Masitinib interrupted the PDGF-induced autophosphorylation of PDGFR and resulted in inhibition of feline ISS proliferation in a dose-dependent manner. Although a possible role exists for masitinib in the management of cats with ISS, the values in this study may correspond with drug concentrations that are too toxic, and further pharmacokinetic studies are needed.
The class of drugs known as tyrosine kinase inhibitors is under evaluation as potential treatment for many tumor types, as they may allow for inhibition of several cancer-signaling pathways, including PDGF inhibition. These drugs can improve treatment of canine mast cell disease when specific mutations are identified. Future use of masitinib or toceranib may allow additional therapeutic intervention against many different neoplastic and nonneoplastic diseases. However, caution should be exercised, as in vitro data did not always translate to in vivo benefit, but anecdotal reports among oncologists supported clinical response in several tumor types with this class of drug.—J. A. Impellizeri, DVM, DACVIM (Oncology)
Masitinib demonstrates anti-proliferative and pro-apoptotic activity in primary and metastatic feline injection-site sarcoma cells. Lawrence J, Saba C, Gogal Jr R, et al. VET COMP ONCOL 10:143-154, 2012.