Introduction: Rationale for Precision Medicine Clinical Trials

Abstract

A normal cell becomes a cancer cell following successive genomic alterations. Cancer is therefore considered as a genomic disease. 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 than cytotoxic agents and have been developed per tumor types and histologies. The occurrence of similar molecular alterations across various tumor types is well described, although their incidences and functional impacts 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 precision approach can today be addressed in clinical trials, since major advances in high throughput technologies allow depicting most druggable molecular alterations for an affordable cost and in a time compatible with clinical practice. Clinical trials using high throughput technologies have been initiated with the aim to evaluate this precision medicine approach in oncology. Some of these trials may not always be able to evaluate the efficacy of drugs in specific subgroups of patients but only the efficiency of the treatment algorithm based on genomic alterations.