We propose a potential prevention strategy of RRM1 through shunting glucose-derived carbon between glucose catabolism and pentose phosphate pathway and reveal the blocking mechanism of RRM1 on glucose catabolism works by a phosphorylation-independent mechanism on PKM2 as shown in Fig. 1K. The multifaceted role of RRM1 in cell metabolism and cell cycle progression makes it a valuable target to improve the clinical efficacy of ESCC chemotherapy. The gene discussed is PKM; the disease is esophageal squamous cell carcinoma.