In fact, CRCs harboring mutant RAS/RAF or SPOP can be more effectively killed by drug combinations through catastrophic ISR associated with features of immunogenic cell death (He et al., 2013; He et al., 2016a; He et al., 2016b; Li et al., 2017; Tan et al., 2019), which is believed to help achieve more durable cancer control in patients (Ruan et al., 2020). This evidence concerns the gene SPOP and cancer.