Given that ERK and ferroptosis are involved in either regulating or relaying ESSENCE activity, respectively, it lends credence to the possibility that a combined therapeutic approach targeting EGFR–ERK activation (selumetinib) along with the induction of ferroptosis (sulfasalazine) could yield superior outcomes in treating ESSENCE-high CRC. The gene discussed is EGFR; the disease is colorectal carcinoma.