IGF-1R signaling activates the PI3K/AKT survival pathway and is involved in resistance to EGFR and HER2 inhibitors.[160, 161] Likewise, resistance to anti-IGF-1R therapies is mediated by HER3/HRG signaling.[162] In fact, MM-141 overcame resistance to anti-IGF-1R therapies and improved anti-tumor responses in preclinical models.[163] The safety profile of MM-141 was established in a phase I trial and an ongoing study is evaluating combination with gemcitabine and nab-paclitaxel in metastatic pancreatic cancer (NCT02399137) (Table 6).[164]. The gene discussed is HRG; the disease is neoplasm.