Abstract
Despite their different histological and molecular properties, different types of cancers share few essential functional alterations. Some of these cancer hallmarks may easily be studied in in vitro cultures, while others are related to the way in which tumors grow in vivo.
According to the systems biology paradigm, complex cellular functions arise as system-level properties from the dynamic interaction of a large number of biomolecules. We previously newly defined four basic cancer cell properties derived from known cancer hallmarks amenable to system-level investigation in cell cultures: enhanced growth, altered response to apoptotic cues, genomic instability and inability to enter senescence following oncogenic signaling.
Here we summarize the major properties of enhanced growth that is dependent on metabolism rewiring - in which glucose is mostly used by fermentation while glutamine provides nitrogen and carbon atoms for biosyntheses – and controlled by oncogene signaling. We then briefly review the major drugs used to target signaling pathways in preclinical and clinical studies, whose clinical efficacy is unfortunately severely limited by tumor resistance, substantially due to signaling cross-talk.
We present a systems biology roadmap that integrates different types of mathematical models with conventional and post-genomic biomolecular analyses that will provide a deeper mechanistic understanding of the links between metabolism and uncontrolled cancer cell growth. This approach is taken to be instrumental both in unraveling cancer’s first principles and in designing novel drugs able to target one or more control or execution steps of the cancer rewired metabolism, in order to achieve permanent arrest of tumor development.
Keywords: Model, metabolic rewiring, glutamine, Warburg effect.
Current Pharmaceutical Design
Title:A Systems Biology Road Map for the Discovery of Drugs Targeting Cancer Cell Metabolism
Volume: 20 Issue: 15
Author(s): Lilia Alberghina, Daniela Gaglio, Rosa Maria Moresco, Maria Carla Gilardi, Cristina Messa and Marco Vanoni
Affiliation:
Keywords: Model, metabolic rewiring, glutamine, Warburg effect.
Abstract: Despite their different histological and molecular properties, different types of cancers share few essential functional alterations. Some of these cancer hallmarks may easily be studied in in vitro cultures, while others are related to the way in which tumors grow in vivo.
According to the systems biology paradigm, complex cellular functions arise as system-level properties from the dynamic interaction of a large number of biomolecules. We previously newly defined four basic cancer cell properties derived from known cancer hallmarks amenable to system-level investigation in cell cultures: enhanced growth, altered response to apoptotic cues, genomic instability and inability to enter senescence following oncogenic signaling.
Here we summarize the major properties of enhanced growth that is dependent on metabolism rewiring - in which glucose is mostly used by fermentation while glutamine provides nitrogen and carbon atoms for biosyntheses – and controlled by oncogene signaling. We then briefly review the major drugs used to target signaling pathways in preclinical and clinical studies, whose clinical efficacy is unfortunately severely limited by tumor resistance, substantially due to signaling cross-talk.
We present a systems biology roadmap that integrates different types of mathematical models with conventional and post-genomic biomolecular analyses that will provide a deeper mechanistic understanding of the links between metabolism and uncontrolled cancer cell growth. This approach is taken to be instrumental both in unraveling cancer’s first principles and in designing novel drugs able to target one or more control or execution steps of the cancer rewired metabolism, in order to achieve permanent arrest of tumor development.
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Cite this article as:
Alberghina Lilia, Gaglio Daniela, Moresco Maria Rosa, Gilardi Carla Maria, Messa Cristina and Vanoni Marco, A Systems Biology Road Map for the Discovery of Drugs Targeting Cancer Cell Metabolism, Current Pharmaceutical Design 2014; 20 (15) . https://dx.doi.org/10.2174/13816128113199990490
DOI https://dx.doi.org/10.2174/13816128113199990490 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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