Researchers identified a novel multikinase receptor inhibitor called vorolanib that has potent antiangiogenic and antitumor properties, as published in Molecular Therapy: Oncolytics.

The novel kinase receptor inhibitor is also potentially less toxic compared to other similar kinase inhibitors like sunitinib and could be a new therapeutic agent for different cancers including gastrointestinal stromal tumors (GISTs).

“Several clinical trials using vorolanib, alone or in combination with other therapeutic agents, are being conducted to investigate its anti-cancer effects in patients with advanced solid tumors,” the researchers wrote. 


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Preclinical studies in rats have shown that vorolanib reduces choroidal neovascularization and had competitive binding and inhibitory activities with kinase insert domain receptor, platelet-derived growth factor receptor beta, fms-like tyrosine kinase 3, and C-Kit.

It also inhibited rearranged during transfection and AMP-activated protein kinase 1 more than sunitinib. This indicates that it has more stringent kinase selectivity, the researchers said. Moreover, they showed that vorolanib inhibited the proliferation of human umbilical vein endothelial cells induced by vascular endothelial growth factor in vitro.

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Using mouse xenograft models, they showed that vorolanib could inhibit the growth of MV-4-11, A549, 786-O, HT-29, BxPC-3, and A375 cells in a dose-dependent manner with no significant toxicities. In the particular case of the MV-4-11 xenograft model, vorolanib led to complete tumor regression.

GISTs are a rare type of cancer originating from the mesenchymal cells in the gastrointestinal tract. The first-line medical treatment for GIST is the tyrosine kinase inhibitor imatinib mesylate. For patients who cannot tolerate imatinib mesylate, or for whom the treatment is no longer effective, sunitinib can be used as a second-line treatment.

There are also third and fourth-line tyrosine kinase inhibitors that have been approved by the US Food and Drug Administration or that are being investigated for the treatment of patients with GIST who cannot tolerate or are no longer responding to the existing options. Vorolanib could be a therapeutic agent.

Reference

Liang C, Yuan X, Shen Z, Wang Y, Ding L. Vorolanib, a novel tyrosine receptor kinase receptor inhibitor with potent preclinical anti-angiogenic and anti-tumor activity. Molecular Therapy: Oncolytics. Published online January 10, 2022. doi:10.1016/j.omto.2022.01.001