Genomics is having a major impact on therapeutics development in medicine. In oncology, the impact is particularly profound. Cancer is a set of diseases resulting from DNA alterations, and each tumor is almost unique with regard to the somatic alterations that it harbors. In fact, not only do any two tumors differ with regard to their DNA alterations but each tumor is composed of subclones of cells, and the subclones differ from each other with regard to their mutational spectrum. Although the discovery of these DNA changes provides a rich source of potential molecular targets, the development and evaluation of therapeutics based on re-regulating these targets poses profound challenges, many of which are the topic of this monograph.

Our focus will be heavily on oncology, where the personalization of therapy is primarily based on the tumor DNA genome that has undergone somatic alterations. The material here should be of value, however, in the study of other diseases for which the candidate characteristics for disease personalization are often based on germ line polymorphisms or phenotypic measures of disease heterogeneity.

The randomized clinical trial has been a fundamentally important contribution to medicine. Randomized clinical trials have permitted us to distinguish the minority of new regimens that are effective from the majority of proposed interventions that are ineffective, harmful, and expensive. The history of medicine contains many examples of harmful treatments that persisted for decades based on erroneous expert opinion. Clinical trials attempt to make the opinion of medical authorities evidence based.