Similar to this EGFR/HER2-independent role in NF-κB activation, lapatinib has also been reported to up-regulate the expression of pro-apoptotic TRAIL death receptors DR4 and DR5 through an off-target mechanism in colon cancer cells and, thus, sensitizes these cancer cells to TRAIL-induced apoptosis [21]. The gene discussed is TNFRSF10B; the disease is malignant colon neoplasm.