Standardizing Fn detection by fecal qPCR or tumor FISH can be used to divide patients into two groups: Fn-high and Fn-low, for trial enrolment; phase-II/III studies should now combine KRAS-G12C ± anti-EGFR strategies with Fn-directed modulators such as bacteriophage cocktails, Fap2-targeted polymers, or AMP-114 peptides, while also considering the longitudinal microbiome and circulating tumor DNA profiling, track response, and resistance. The gene discussed is EGFR; the disease is neoplasm.