Precision medicine and oncology: an overview of the opportunities presented by next-generation sequencing and big data and the challenges posed to conventional drug development and regulatory approval pathways.

Recent studies have begun to describe the vast extent of interand intra-tumor genomic diversity and the ability of the tumor genome to evolve over time and in response to selective pressures exerted by therapy, Gerlinger et al [1], Greaves and Maley [2]. Techniques allowing the systematic evaluation of the tumor genome, particularly Next-Generation Sequencing (NGS), now have performance characteristics and costs which allow them to be integrated into routine clinical care and drug development, Frampton et al [3]. It is therefore pertinent to reevaluate the drug development and approval process of oncology therapies in light of these developments. Although it is too early to predict the extent to which NGS will transform oncology, it will likely become an important tool in routine diagnostics and, when combined with the use of treatment/matching algorithms based on the clinical relevance of mutational profiles, will have a beneficial effect on patient outcomes. Along with advances in immunotherapy, NGS, as a basis of selecting targeted therapies for cancer patients, should be incorporated into strategic planning for the future of oncology drug development. In the future, integrative systems biology approaches encompassing epigenomics, pathway analysis, and insights derived from the tumor microenvironment, in addition to genomics, are expected to lead to improved decision making. The use of NGS to elucidate the impact of somatic genomic alterations on treatment outcomes is an important first step, even if current attempts 1 Algorithms in this context refer to either simple decision rules, such as those embodied in clinical guidelines or more complex decision rules, which require the use of computer supported decision support systems. at T uane U niersity M eical L irary on A ril 7, 2016 http://annofordjournals.org/ D ow nladed from