Toward personalized cancer nanomedicine - past, present, and future.

Tumors are composed of highly proliferate, migratory, invasive, and therapy-evading cells. These characteristics are conferred by an enormously complex landscape of genomic, (epi-)genetic, and proteomic aberrations. Recent efforts to comprehensively catalogue these reversible and irreversible modifications have began to identify molecular mechanisms that contribute to cancer pathophysiology, serve as novel therapeutic targets, and may constitute biomarkers for early diagnosis and prediction of therapy responses. With constantly evolving technologies that will ultimately enable a complete survey of cancer genomes, the challenges for discovery cancer science and drug development are daunting. Bioinformatic and functional studies must differentiate cancer-driving and -contributing mutations from mere bystanders or 'noise', and have to delineate their molecular mechanisms of action as a function of collaborating oncogenic and tumor suppressive signatures. In addition, the translation of these genomic discoveries into meaningful clinical endpoints requires the development of co-extinction strategies to therapeutically target multiple cancer genes, to robustly deliver therapeutics to tumor sites, and to enable widespread dissemination of therapies within tumor tissue. In this perspective, I will describe the most current paradigms to study and validate cancer gene function. I will highlight advances in the area of nanotechnology, in particular, the development of RNA interference (RNAi)-based platforms to more effectively deliver therapeutic agents to tumor sites, and to modulate critical cancer genes that are difficult to target using conventional small-molecule- or antibody-based approaches. I will conclude with an outlook on the deluge of challenges that genomic and bioengineering sciences must overcome to make the long-awaited era of personalized nano-medicine a clinical reality for cancer patients.