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Systems Biology Approach to Metabolomics in Cancer Studies

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Systems Biology in Cancer Research and Drug Discovery

Abstract

The astonishing development of high-throughput techniques in the last decades has fostered a renewed, dynamic comprehension of cell and tissue metabolism, giving unexpected insights into the ‘systemic aspects’ of cancer, namely pointing out that metabolism should be considered a truly “systems property”. Both internal and microenvironmental cues tightly cooperate in shaping the tissue metabolomic fingerprint. Tumour metabolome hardly could be mechanistically linked to the linear dynamics of few gene regulatory networks thus, it is more likely to be the complex end point of several interacting non-linear pathways, involving both cells and their microenvironment. As such, tumour metabolism might be considered an emerging, “systems property”, arising at the integrated scale of the whole system and behaving like an “attractor” in a specific space phase defined by thermodynamic constraints.

Therefore, metabolomics ‘strategies’ are settled in order to understand complex biological systems from an integrated (‘holistic’) point of view. Metabolomics measurements are hence correlated with the time-dependent changes in concentrations of other components (proteins, gene-expression data), in order to obtain an integrated model of the gene-protein-metabolite interactions. Such framework represents a meaningful discontinuity with respect to the reductionist and qualitative molecular biology, and discloses new perspectives to scientific research.

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Abbreviations

FDG-PET:

2-Fluoro-2-deoxy-D-glucose-positron emission tomography

ATP:

Adenosine triphosphate

LDH:

Lactate dehydrogenase

HK:

Hexokinase

AcCoA:

Acetyl-CoA

OAA:

Oxalacetate

AMPK:

AMP-activated protein kinase

GLUT-1:

Glucose transporter

PGK-1:

Phosphoglycerate kinase

NBE:

Normalized bending energy

MCA:

Metabolic control analysis

G6P:

Glucose 6 phosphate

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Authors and Affiliations

  1. Department of Experimental Medicine, La Sapienza University, Viale Regina Elena 324, 00161, Rome, Italy

    Mariano Bizzarri

  2. Department of Clinical and Molecular Medicine, La Sapienza University, Piazza Sassari 3, 00161, Rome, Italy

    Simona Dinicola

  3. Department of Chemistry, La Sapienza University, Piazzale Aldo Moro 5, 00185, Rome, Italy

    Cesare Manetti

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  1. Mariano Bizzarri
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  2. Simona Dinicola
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  3. Cesare Manetti
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Correspondence to Mariano Bizzarri .

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  1. Karmanos Cancer Institute, Wayne State University, Detroit, MI, USA

    Asfar S. Azmi

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Bizzarri, M., Dinicola, S., Manetti, C. (2012). Systems Biology Approach to Metabolomics in Cancer Studies. In: Azmi, A.S. (eds) Systems Biology in Cancer Research and Drug Discovery. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-4819-4_1

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