Precision medicine: an approach to R&D for delivering superior medicines to patients

Precision Medicine [1,2] is an approach to discovering and developing medicines and vaccines that deliver superior outcomes for patients, by integrating clinical and molecular information to understand the biological basis of disease. This approach leads to better selection of disease targets and identification of patient populations that experience better clinical outcomes. Ultimately, the potential of Precision Medicine is that it will yield treatments that deliver clinically significant treatment effects, with favorable safety profiles. When appropriate, these new treatments are focused on a particular sub- group of patients with certain genotypic and/or phenotypic characteristics that make them more likely to benefit or less likely to experience side effects. A related concept, “Personalized Medicine”, has been defined by President’s Council of Advisors on Science and Technology (PCAST) as “the tailoring of medical treatment to the individual characteristics of each patient to classify individuals into subpopulations that differ in their susceptibility to a particular disease or their response to a specific treatment [3]”. Thus, products and diagnostics developed through Precision Medicine facilitate the practice of Personalized Medicine.Oncology is the frontier of Precision Medicine and typically focus is on identification of gene fusions (e.g. crizotinib, an ALK inhibitor for ALK fusion proteins in lung cancer), mutations (as in the case of vemurafinib, a BRAF inhibitor for melanoma patients with the BRAF V600E mutation) and protein over- expression (e.g. Trastuzumab a HER2-targeted antibody for breast cancer). Crizotinib was identified in 2005 as a cMET (and ALK/ROS1) kinase inhibitor. In 2007, contemporaneously with dose escalation in Phase I studies, academic researchers in Japan found that about 5% of patients with non-small cell lung cancer (NSCLC), typically younger non-smokers, carry an EML4-ALK fusion gene leading to constitutive activation of ALK kina