HER3 has been found to have an important role in resistance to EGFR-TKIs in NSCLC.56,57 Studies have revealed that an important mechanism resulting in resistance to EGFR-TKI therapy could be the compensatory upregulation of HER3 along with the sustained PI3K/AKT signaling.58,59 Because HER3 lacks kinase activity, targeting HER3 with a blocking antibody becomes a potential strategy being tested in current preclinical studies in cancer patients.60–62 Several phase I studies to evaluate monoclonal antibodies targeting HER3, such as patritumab, lumretuzumab, SAR256212 or LJM716, are ongoing. The gene discussed is AKT1; the disease is cancer.