Normal cellular survival is dependent on the cooperative expression of genes' signaling through a broad array of DNA patterns. Cancer, however, has an Achilles' heel. Its altered cellular survival is dependent on a limited subset of signals through mutated DNA, possibly as few as three. Identification and control of these signals through the use of RNA interference (RNAi) technology may provide a unique clinical opportunity for the management of cancer that employs genomic-proteomic profiling to provide a molecular characterization of the cancer, leading to targeted therapy customized to an individual cancer signal. Such an approach has been described as "personalized therapy." The present review identifies unique developing technology that employs RNAi as a method to target, and therefore block, signaling from mutated DNA and describes a clinical pathway toward its development in cancer therapy.