Just so stories: The random acts of anti-cancer nanomedicine performance

Contrary to high expectations, the majority of clinically approved anti-cancer nanomedicine, and those under clinical trials, have shown limited therapeutic efficacy in humans. So, why these nanomedicine are not delivering their promise? Here, we discuss likely factors, and call for a paradigm shift in approach and design of future cancer nanotherapeutics based on realistic cancer models representing human disease, and better understanding of integrated pathophysiological processes, including systems immunology, that modulate human tumor functionality and growth. From the Clinical Editor: This critical review of the current state of translational oncology research utilizing nanomedicine-based approaches provides a comprehensive discussion of the multiple factors that are responsible for poor outcomes when translating these approaches models to the actual human disease.