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Tackling Complex Cancer Questions with Systems Biology

Cancer is a complex disease system involving multiple molecular, genetic, and cellular events. From its early initiation through progression and metastasis, cancer can adapt and evolve as a result of both internal and external signals. These properties make cancer difficult to predict, prevent, and treat. There has been significant progress in characterizing the genetics of cancer, as well as the downstream effects on the molecular and cellular pathways that are critical for the initiation and progression of cancer. However, studies focused on the role of one gene have highlighted the need to understand cancers as integrated systems of genes, networks, and intercellular interactions.

Cancer systems biology is uniquely poised to address the complexity associated with cancer through its unique integration of experimental biology and computational and mathematical analysis. Instead of viewing cancer through the lens of a single mutation or alteration, the goal of cancer systems biology is to provide a birds eye view of the changing cancer ecosystem, thus allowing cancer biologists and oncologists to understand and predict how one alteration effects an entire tumor system.The multidisciplinary Cancer Systems Biology Consortium, funded by the National Cancer Institute, aims to tackle the most perplexing issues in cancer to increase our understanding of tumor biology, treatment options, and patient outcome.

Impact of Cancer Systems Biology

There has been an explosion in the quantity of available experimental data from high-throughput technologies, such as genomic sequencing, transcriptomics, metabolomics, and proteomics. Additionally, targeted experiments on a smaller scale have provided important information about complex interactions within and between cells. Systems analyses and predictive modeling are necessary to integrate across these datasets that span different length and time scales to convert them into knowledge. For ten years from 2004-2014, the National Cancer Institute supported the Integrative Cancer Biology Program (ICBP), a precursor to the current Cancer Systems Biology Consortium. The ICBP brought together cancer biologists and oncologists with computer scientists, mathematicians, and engineers to tackle important cancer questions including the identification of tumor master transcriptional regulators, the role of microRNAs in cancer progression and metastasis, the development of drug resistance in heterogeneous tumor contexts, and optimization of combination therapies for cancer treatment. It is envisioned that the successes of cancer systems biology will encourage investigators to bring these tools to bear on emerging and difficult cancer questions that will require a systems approach to fully comprehend.

 

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number U24CA209923. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.