Interestingly, ER stress is involved in 5‐FU resistance in human colon cancer cells, and knockdown of ER stress‐related proteins GPR78 and ATF6 improved the chemosensitivity.[34] In contrast to their findings, our in vitro (Figure 6H) and in vivo (Figure 7E) evidence showed that the NK‐1R antagonists overcame the 5‐FU resistance by further enhancing the PERK‐eIF2a‐ATF4‐CHOP ER stress signaling. Here, EIF2AK3 is linked to malignant colon neoplasm.