Neuroblastoma is a
malignancy arising from the developing sympathetic nervous system and the most common and deadly
cancer of infancy. New
therapies are needed to improve the prognosis for high-risk patients and to reduce toxicity and late effects.
Spleen tyrosine kinase (SYK) has previously been identified as a promising drug target in various inflammatory diseases and
cancers but has so far not been extensively studied as a potential therapeutic target in
neuroblastoma. In this study, we observed elevated SYK gene expression in
neuroblastoma compared to neural crest and benign
neurofibroma. While SYK
protein was detected in the majority of examined
neuroblastoma tissues it was less frequently observed in
neuroblastoma cell lines. Depletion of SYK by
siRNA and the use of small molecule SYK inhibitors significantly reduced the cell viability of
neuroblastoma cell lines expressing SYK
protein. Moreover, SYK inhibition decreased ERK1/2 and Akt phosphorylation. The SYK inhibitor BAY 613606 enhanced the effect of different chemotherapeutic drugs. Transient expression of a constitutive active SYK variant increased the viability of
neuroblastoma cells independent of endogenous SYK levels. Collectively, our findings suggest that targeting SYK in combination with conventional
chemotherapy should be further evaluated as a treatment option in
neuroblastoma.