*Article* **Effects of Sunitinib and Other Kinase Inhibitors on Cells Harboring a** *PDGFRB* **Mutation Associated with Infantile Myofibromatosis**

**Martin Sramek 1,2,3, Jakub Neradil 1,2,3, Petra Macigova 1,2, Peter Mudry 2, Kristyna Polaskova 2,3, Ondrej Slaby 4, Hana Noskova 4, Jaroslav Sterba 2,3 and Renata Veselska 1,2,3,\***


Received: 1 August 2018; Accepted: 29 August 2018; Published: 1 September 2018

**Abstract:** Infantile myofibromatosis represents one of the most common proliferative fibrous tumors of infancy and childhood. More effective treatment is needed for drug-resistant patients, and targeted therapy using specific protein kinase inhibitors could be a promising strategy. To date, several studies have confirmed a connection between the p.R561C mutation in gene encoding platelet-derived growth factor receptor beta (PDGFR-beta) and the development of infantile myofibromatosis. This study aimed to analyze the phosphorylation of important kinases in the NSTS-47 cell line derived from a tumor of a boy with infantile myofibromatosis who harbored the p.R561C mutation in PDGFR-beta. The second aim of this study was to investigate the effects of selected protein kinase inhibitors on cell signaling and the proliferative activity of NSTS-47 cells. We confirmed that this tumor cell line showed very high phosphorylation levels of PDGFR-beta, extracellular signal-regulated kinases (ERK) 1/2 and several other protein kinases. We also observed that PDGFR-beta phosphorylation in tumor cells is reduced by the receptor tyrosine kinase inhibitor sunitinib. In contrast, MAPK/ERK kinases (MEK) 1/2 and ERK1/2 kinases remained constitutively phosphorylated after treatment with sunitinib and other relevant protein kinase inhibitors. Our study showed that sunitinib is a very promising agent that affects the proliferation of tumor cells with a p.R561C mutation in PDGFR-beta.

**Keywords:** infantile myofibromatosis; receptor tyrosine kinases; platelet-derived growth factor receptor; protein kinase inhibitors; sunitinib; erlotinib; FR180204; U0126; targeted therapy
