Abstract

In oncology, genomics has practically entered the clinic with the emergence of molecularly targeted agents. Some of these drugs have been approved with a companion diagnostic based on a specific genomic molecular alteration. However, molecularly targeted agents have followed the same clinical development as chemotherapeutic agents and have been developed in selected tumor types and histologies. The occurrence of the same molecular alteration across various tumor types is well described, although the incidence and functional impact may vary. The latter raises the question of whether treatment decision in the future should be entirely based on molecular biology, independently of tumor location and histology. This approach can today be addressed in clinical trials, since major advances in high throughput technologies now make it possible to depict most druggable molecular alterations for an affordable cost in a time that is compatible with clinical practice. Studies using high throughput technologies have been initiated with the aim of personalizing therapy in oncology. They include two distinct types of clinical trials: 1) stratified clinical trials according to either molecular alterations or tumor types that still evaluate drug’s efficacy in well-defined patient populations, and 2) algorithm-based trials evaluating treatment algorithm efficiency instead of drugs efficacy. Multiple challenges are associated with these trials in personalized medicine.