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Systems Biology of Pancreatic Cancer: The Role of Tumor-Microenvironment Communication in Development, Progression and Therapy Resistance

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Systems Biology in Cancer Research and Drug Discovery

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Abstract

Pancreatic cancer is an aggressive and highly lethal disease, with a reported 5-year survival of ∼5 %. It comprises the fourth most common cause of malignancy-related death in Western countries and the annual death rate due to this disease approximates its annual incidence rate, which is estimated to be ∼10 cases per 100,000 population. Although there have been some advancements in surgical techniques and adjuvant therapeutic regimens, the survival has not substantially improved in the past 30 years. Pancreatic cancer is characterized by late diagnosis, aggressive local invasion, early systemic dissemination and resistance to chemo- and radiotherapy. Therefore, a better understanding of cellular and molecular mechanisms governing the resistant phenotype of this devastating disease is urgently needed. Systems biology has emerged as one of the most promising approaches to understand the complexities of tumor-microenvironment interplay on a quantitative multi-scale level, i.e. by incorporating genomics, transcriptomics, proteomics, epigenomics and functional genomics studies. Integrative analysis of these data aims to dissect inter- and intracellular networks critically contributing to tumor progression and therapy resistance.

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Abbreviations

PDAC:

Pancreatic ductal adenocarcinoma

PSC:

Pancreatic stellate cells

ECM:

Extracellular matrix

MDM2:

Murine double minute 2 protein

ENT1:

Equilibrative nucleoside transporter 1

ENT2:

Equilibrative nucleoside transporter 2

CNT1:

Concentrative nucleoside transporters

CNT2:

Concentrative nucleoside transporters

VEGF:

Vascular endothelial growth factor

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Acknowledgments

This work was supported in part by the German Krebshilfe (Deutsche Krebshilfe, Max-Eder 108876), DFG National Priority Research Program: the Tumor-Vessel Interface “SPP1190” and KFO214, and the German Federal Ministry of Research and Technology (Bundesministerium für Bildung und Forschung – BMBF 03NUK004C).

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Authors and Affiliations

  1. Molecular RadioOncology, Heidelberg Ion Therapy Center (HIT), University of Heidelberg Medical School & National Center of Tumour Diseases (NCT), German Cancer Research Center (DKFZ), Heidelberg, Germany

    Sara Chiblak, Fevzi Demircioglu, Azadeh Fahim Golestaneh & Amir Abdollahi

  2. Center of Cancer Systems Biology, St. Elizabeth’s Medical Center, Department of Medicine, Tufts University, Boston, MA, USA

    Amir Abdollahi

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  1. Sara Chiblak
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  2. Fevzi Demircioglu
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  3. Azadeh Fahim Golestaneh
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  4. Amir Abdollahi
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Correspondence to Amir Abdollahi .

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

    Asfar S. Azmi

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© 2012 Springer Science+Business Media Dordrecht

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Chiblak, S., Demircioglu, F., Golestaneh, A.F., Abdollahi, A. (2012). Systems Biology of Pancreatic Cancer: The Role of Tumor-Microenvironment Communication in Development, Progression and Therapy Resistance. 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_6

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