IGF1 and neoplasm: When the drug is in the “off-target” state, tumor resistance to the drug is primarily associated with signaling pathway interactions [52], such as between hepatocyte growth factor (HGF)/c-MET, vascular endothelial growth factor (VEGF), insulin-like growth factor 1 (IGF1), signal transducers and activators of transcription (STAT)3, and paracrine pathways [53].