Definition

An orally bioavailable selective inhibitor of the proto-oncogene receptor tyrosine kinase rearranged during transfection (RET), with potential antineoplastic activity. Upon oral administration, RET inhibitor APS03118 selectively targets and binds to wild-type RET and various RET fusions and mutations, including, but not limited to, solvent front mutations (SFMs) RET G810C/S/R and the gatekeeper RET V804 mutation, thereby inhibiting the activity of RET. This results in an inhibition of cell growth of tumors that exhibit increased RET activity due to these fusions and mutations. RET overexpression, activating mutations, and fusions result in the upregulation and/or overactivation of RET tyrosine kinase activity in various cancer cell types. Dysregulated RET activity plays a key role in the development and progression of certain cancers. Solvent front and gatekeeper resistance mutations play a key role in acquired tumor resistance to RET inhibitors.