Cancer Systems Biology: a peek into the future of patient care?

Abstract

Traditionally, scientific research has focused on studying individual events, such as single mutations, gene function, or the effect that mutating one protein has on a biological phenotype. A range of technologies is beginning to provide information that will enable a holistic view of how genomic and epigenetic aberrations in cancer cells can alter the homeostasis of signalling networks within these cells, between cancer cells and the local microenvironment, and at the organ and organism level. This process, termed Systems Biology, needs to be integrated with an iterative approach wherein hypotheses and predictions that arise from modelling are refined and constrained by experimental evaluation. Systems biology approaches will be vital for developing and implementing effective strategies to deliver personalized cancer therapy. Specifically, these approaches will be important to select those patients who are most likely to benefit from targeted therapies and for the development and implementation of rational combinatorial therapies. Systems biology can help to increase therapy efficacy or bypass the emergence of resistance, thus converting the current-often short term-effects of targeted therapies into durable responses, ultimately to improve patient quality of life and provide a cure.

Figure 1. Application of cancer systems biology to decipher complex interactions in multiple dimensions

This figure shows the complexity of interactions between different molecular networks within the cell that regulate the multitude of cellular functions. The intracellular machinery must coordinate with surrounding cells and the extracellular microenvironment to achieve homeostasis. Working within the body as a whole, each of these physiologically functional units is tightly coupled and regulated. Accumulated aberrations at the molecular level can decouple any one of these complex interactions and lead to a neoplastic phenotype. The promise of cancer systems biology is the ability to integrate these multi-scale characteristics into cohesive predictive models that can uncover emergent properties to be used in making cancer history.

Figure 2. Integrating tumour molecular characteristics with pharmacogenomics for precision

Cancer systems biology can bridge the vast amount of molecular characteristics of the tumour with pharmacogenomics to deliver on the promise of personalized therapy. The use of systems models to integrate patient specific data sets with drug response profiles can enable the prediction of effective patient-specific therapeutic options.