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Systems biology and cancer cachexia

Gallagher, Iain and Jacobi, Carsten and Tardif, Nicolas and Fearon, Kenneth (2016) Systems biology and cancer cachexia. Special Issue of SCDB .

Abstract

Introduction
Cancer cachexia is a complex syndrome: at its core is the interaction between the host and cancer cells. This interaction takes place against a background of treatment with attendant efficacy and/ or toxicity. As a result of this interaction, a variety of cellular and soluble mediators are activated which act together with the neuro-endocrine system to induce changes in systemic metabolism and food intake with consequent changes in the mass and function of a variety of organs and tissues. In turn, these changes result in the symptoms and signs experienced by the patient that ultimately leads to altered quality and quantity of life [1]. The complexity of cancer cachexia in humans is increased by the relatively slow pace of evolution of cancer and its complications (developing over months or years) and that implicit in this timescale is the possibility for adaptation. Such adaptation can be present in one component of a tissue but not in another so that the cellular events of atrophy and regeneration may be present simultaneously. Equally, cancer is generally a disease of old age and patients can have multiple co-morbidities, all influencing tissue metabolism but not necessarily linked to cancer-associated tissue loss.
Clearly the best way to cure cachexia is to cure the cancer as this would resolve all domains of this multi-layered process. Unfortunately, for patients with the common advanced solid epithelial malignancies this is not a realistic goal. The next priority would be to inhibit key mediators. However, the heterogeneity of these mediators and the redundancy within activated cascades has meant that treatments that target single mediators have not proved clinically successful (e.g. anti-TNF antibody therapy:[2]). The third sphere of intervention is to target mechanisms rather than mediators. It is the attempt to understand key mechanisms that could be turned into therapeutic targets that makes systems biology important to cancer cachexia. Given the inherent heterogeneity in patient samples, any attempt to use systems biology requires a rigorous approach to cohort design/phenotype classification [3]. Whilst it would be interesting to discuss the whole spectrum of tissues involved in the cachexia process, for the purposes of this review, the primary focus will be on skeletal muscle atrophy.
Overview of Systems Biology
In the last decade the traditional approach to understanding the development of disease used a focused approach: one “omics”-technology at a time. After the deciphering of the human genome, it was evident that the development and manifestation of disease cannot be explained by the nature of the genome alone. By focusing on one “omics” technology at a time, only one piece of the whole puzzle becomes visible. The basic idea of systems biology is to use a holistic approach to deciphering the complexity of biological systems. With newer technologies like RNA deep-sequencing, SNP-analysis, metabolomics or SWATH analysis, a much more detailed picture can be generated. Deeper understanding of health or disease cannot be achieved if the different technologies are used separately, but rather when approaches are combined.

Item Type: Article
Date Deposited: 26 Apr 2016 23:45
Last Modified: 26 Apr 2016 23:45
URI: https://oak.novartis.com/id/eprint/27621

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