As POLQ depletion also impairs the repair of DNA damage induced by multiple agents, we hypothesize that the double KO of POLQ and FANCD2 gravely impairs the repair efficiency of DNA DSBs and promotes the genomic instability in ESCC to suppress ESCC cell proliferation in a synthetic lethal pattern. The gene discussed is POLQ; the disease is esophageal squamous cell carcinoma.