Thus, the combinatorial treatment strategy of (i) KRAS G12C-mutant inhibitors and (ii) RNA polymerase I machinery inhibitors, such as CX-3543 and CX-5461, could be a possible strategy to tackle resistance and has to be studied in in vitro and in vivo settings, which promotes the increased therapeutic treatment of KRAS G12C-mutated cancers in the era of precision medicine. This evidence concerns the gene KRAS and cancer.