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Disrupting cancer cells’ biocircuits with interactome-based drugs: is ‘clinical’ innovation realistic?

Despite expectations, abundant scientific and clinical evidence now reveals that current reductionist science and single pathway-based cancer-targeted drugs provide isolated clinical success. Overall, efficacy is limited with temporary antitumor activity [1]. Can innovation in technology, systems science and genome annotation surpass daunting hurdles for understanding dynamic networks of interacting biological systems to overcome drug resistance? Such a network biology approach paves the way for disrupting signaling biocircuits in cancer cells through next-generation drugs and biomarkers discovery. Network medicine is the most promising emerging approach to cure incurable diseases such as cancer and to overcome unresolved problems such as longevity [2,3]. To reach this future goal, not only is the understanding of complex dynamic signaling transduction networks that drive crucial cellular processes, including cell survival, growth and apoptosis at molecular level required [4,5], but also the exploration and possible prediction of the dynamic spatiotemporal personal genome–lifestyle interaction networks at the whole organism level [6]. Breakthroughs in the high-throughput technologies based on sequencing and arrays methods shape now the high hope of the clinical genome era. Shifting from reductionist biology and genetics to systems medicine by adopting omics data to the clinic is increasingly recognized as a clinical necessity. This effort requires collaboration of both innovators with a clinical orientation and physicians with a translational background and research perspectives [2–6]. Despite major science and technology advances, the crucial debate in the real clinical world is whether the myriad of challenges in understanding and predicting dynamic interacting biological systems, a cell’s decisions to survive or die, and tissue and organ homeostasis can be overcome. This understanding appears to be an essential step for the discovery of signaling network-based drugs and biomarkers to prevent or cure complex multifactorial disorders [6,7]. Although there is scepticism over whether the analysis of the interactome – the whole set of gene, protein and molecule interaction networks driving cell behavior – and discovery of drugs targeting interactome global dysfunction in cancer are realistic goals, current advances in science and technology provide a fascinating strategy for future success. The goal of ‘clinical innovation’, defined here as a revolution in clinical practice for improving healthcare and healthy longevity [3,7], and curing cancer [1,8], in Disrupting cancer cells’ biocircuits with interactome-based drugs: is ‘clinical’ innovation realistic?