Sulfatinib and SPP86 show antitumor activity both in medullary thyroid carcinoma (MTC) cell lines and a zebrafish model of thyroid cancer, a recent study suggests.
Sulfatinib is a multitarget kinase inhibitor selective for fibroblast growth factor receptor-1 (FGFR-1) and the vascular endothelial growth factor receptor (VEGFR) 1, 2, and 3, while SPP86 is a RET-specific inhibitor. SU5402, on the other hand, inhibited cell migration in only 1 of the 2 cell lines.
The researchers found that all 3 molecules decreased the viability of the 2 MTC cell lines that they used. Moreover, sulfatinib and SPP86 significantly induced apoptosis and inhibited migration in both cell lines.
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“Our results suggest a potential role in targeting the FGFR and VEGFR signaling pathways as an alternative strategy for resistant tumors and a significative antitumor activity of this new RET-specific inhibitor,” the authors concluded.
The results were published in the journal Cancers.
MTC is a rare type of neuroendocrine tumor of the thyroid gland arising from the parafollicular cells. Most patients with the disease have a mutation in the RET proto-oncogene.
The treatment of MTC involves 2 tyrosine kinase inhibitors, cabozantinib and vandetanib. However, they can cause severe side effects, and not all patients respond to them.
In the present study, a team of researchers led by Giovanni Vitale, MD, PhD, evaluated the antitumor activity of 3 novel tyrosine kinase inhibitors for the treatment of MTC. These were SU5402, sulfatinib, and SPP86. SU5402 is a selective inhibitor of FGFR-1 and VEGFR-2.
When the investigators used zebrafish embryos grafted with human MTC cells, they found that incubation with sulfatinib and SPP86 led to a significant reduction in MTC cell-induced angiogenesis.
“This work suggests the potential utility of targeting FGFR and VEGFR signaling pathways as an alternative therapy for MTC,” the team concluded.
Reference
Saronni D, Gaudenzi G, Dicitore A, et al. Preclinical evaluation of novel tyrosine-kinase inhibitors in medullary thyroid cancer. Cancers. 2022;14(18):4442. doi:10.3390/cancers14184442
