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Systems Biology of Personalized Medicine

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Bioinformatics for Systems Biology

Abstract

To achieve the promise of individualized molecular-based medicine, the application of informatic tools to the entire hierarchy of biological system interactions and dynamics will be required in order to promote the effective discovery, validation and application of new diagnostic and treatment strategies in a real-time environment. As the field of biomarker discovery continues to unravel the underlying molecular mechanisms of diseases, the utility of the acquired and expanding knowledge lags far behind. Systems Biology represents a pivotal component of the personalized medicine workflow through its ability to consolidate complex data and knowledge into definable networks, and reproducibly identify key convergence/divergence points representing the biomarkers of interest. In this chapter, we will provide a brief update in the field of personalized medicine, and how Systems Biology tools can be used to support biomarker discovery. This chapter emphasizes the potential utility of Systems Biology for the prediction of network-based treatments in oncology, using empirical biomarker data sets in conjunction with knowledge and pre-existing drug resources.

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References

The Challenge – The Complexity of Biological Systems

  1. Stumpf MP, Kelly WP, Thorne T, Wiuf C. Evolution at the system level: the natural history of protein interaction networks. Trends Ecol Evol 2007;22(7):366–373.

    Article  PubMed  Google Scholar 

  2. Huang S. Back to the biology in Systems Biology: what can we learn from biomolecular networks? Brief Funct Genomic Proteomic 2004;2(4):279–297.

    Article  CAS  PubMed  Google Scholar 

  3. van der Greef J, Martin S, Juhasz P, et al. The art and practice of Systems Biology in medicine: mapping patterns of relationships. J Proteome Res 2007;6(4):1540–1559.

    Article  PubMed  Google Scholar 

  4. Fujarewicz K, Kimmel M, Lipniacki T, Swierniak A. Adjoint systems for models of cell signaling pathways and their application to parameter fitting. IEEE/ACM transactions on computational biology and bioinformatics/IEEE, ACM 2007;4(3):322–335.

    Article  CAS  PubMed  Google Scholar 

The Added Complexity of Cancer

  1. Wang E, Lenferink A, O'Connor-McCourt M. Cancer Systems Biology: exploring cancer-associated genes on cellular networks. Cell Mol Life Sci 2007;64(14):1752–1762.

    Article  CAS  PubMed  Google Scholar 

  2. Hanahan D, Weinberg RA. The hallmarks of cancer. In: Cell; 2000:57–70.

    Google Scholar 

  3. Webb CP, Vande Woude GF. Genes that regulate metastasis and angiogenesis. J Neurooncol 2000; 50(1-2):71–87.

    Article  CAS  PubMed  Google Scholar 

  4. Aranda-Anzaldo A. Cancer development and progression: a non-adaptive process driven by genetic drift. Acta Biotheor 2001;49(2):89–108.

    Article  CAS  PubMed  Google Scholar 

  5. Balakrishnan A, Bleeker FE, Lamba S, et al. Novel somatic and germline mutations in cancer candidate genes in glioblastoma, melanoma, and pancreatic carcinoma. Cancer Res 2007;67(8):3545–50.

    Article  CAS  PubMed  Google Scholar 

  6. Sjoblom T, Jones S, Wood LD, et al. The consensus coding sequences of human breast and colorectal cancers. Science 2006;314(5797):268–274.

    Article  PubMed  Google Scholar 

Personalized Medicine – The Objectives

  1. Maron BJ, Hauser RG. Perspectives on the failure of pharmaceutical and medical device industries to fully protect public health interests. Am J Cardiol 2007;100(1):147–151.

    Article  PubMed  Google Scholar 

  2. Goodsaid F, Frueh FW. Implementing the U.S. FDA guidance on pharmacogenomic data submissions. Environ Mol Mutagen 2007;48(5):354–358.

    Article  CAS  PubMed  Google Scholar 

  3. Jain KK. Challenges of drug discovery for personalized medicine. Curr Opin Mol Ther 2006;8(6):487–492.

    CAS  PubMed  Google Scholar 

Biomarkers in Practice – The Role of Systems Biology

  1. Nusbaum R, Isaacs C. Management updates for women with a BRCA1 or BRCA2 mutation. Mol Diagn Ther 2007;11(3):133–44.

    CAS  PubMed  Google Scholar 

  2. Daly AK. Individualized drug therapy. Curr Opin Drug Discov Devel 2007;10(1):29–36.

    CAS  PubMed  Google Scholar 

  3. de Leon J, Susce MT, Murray-Carmichael E. The AmpliChip CYP450 genotyping test: Integrating a new clinical tool. Mol Diagn Ther 2006;10(3):135–151.

    PubMed  Google Scholar 

  4. Marsh S. Impact of pharmacogenomics on clinical practice in oncology. Mol Diagn Ther 2007;11(2):79–82.

    CAS  PubMed  Google Scholar 

  5. Duffy MJ. Role of tumor markers in patients with solid cancers: A critical review. Eur J Intern Med 2007;18(3):175–184.

    Article  CAS  PubMed  Google Scholar 

  6. Thompson IM, Ankerst DP. Prostate-specific antigen in the early detection of prostate cancer. Cmaj 2007;176(13):1853–1858.

    PubMed  Google Scholar 

  7. Webb CP, Pass HI. Translation research: from accurate diagnosis to appropriate treatment. J Transl Med 2004;2(1):35.

    Article  PubMed  Google Scholar 

  8. Pass HI, Lott D, Lonardo F, et al. Asbestos exposure, pleural mesothelioma, and serum osteopontin levels. N Engl J Med 2005;353(15):1564–1573.

    Article  CAS  PubMed  Google Scholar 

  9. Miller LD, Liu ET. Expression genomics in breast cancer research: microarrays at the crossroads of biology and medicine. Breast Cancer Res 2007;9(2):206.

    Article  PubMed  Google Scholar 

  10. Kaklamani VG, Gradishar WJ. Gene expression in breast cancer. Curr Treat Options Oncol 2006;7(2):123–128.

    Article  PubMed  Google Scholar 

  11. Canales RD, Luo Y, Willey JC, et al. Evaluation of DNA microarray results with quantitative gene expression platforms. Nat Biotechnol 2006;24(9):1115–1122.

    Article  CAS  PubMed  Google Scholar 

  12. Rhodes DR, Kalyana-Sundaram S, Tomlins SA, et al. Molecular concepts analyzes links tumors, pathways, mechanisms, and drugs. Neoplasia 2007;9(5):443–454.

    Article  CAS  PubMed  Google Scholar 

  13. O'Donovan N, Crown J. EGFR and HER-2 antagonists in breast cancer. Anticancer Res 2007;27(3A):1285–1294.

    PubMed  Google Scholar 

  14. Tsuda H. HER-2 (c-erbB-2) test update: present status and problems. Breast Cancer 2006;13(3):236–248.

    Article  PubMed  Google Scholar 

  15. Hochhaus A, Erben P, Ernst T, Mueller MC. Resistance to targeted therapy in chronic myelogenous leukemia. Semin Hematol 2007;44(1 Suppl 1):S15–24.

    Article  CAS  PubMed  Google Scholar 

  16. Bublil EM, Yarden Y. The EGF receptor family: spearheading a merger of signaling and therapeutics. Curr Opin Cell Biol 2007;19(2):124–134.

    Article  CAS  PubMed  Google Scholar 

  17. Wen L, Li W, Sobel M, Feng JA. Computational exploration of the activated pathways associated with DNA damage response in breast cancer. Proteins 2006;65(1):103–110.

    Article  CAS  PubMed  Google Scholar 

  18. Schafer R, Schramme A, Tchernitsa OI, Sers C. Oncogenic signaling pathways and deregulated target genes. Recent Results Cancer Res 2007;176:7–24.

    Article  PubMed  Google Scholar 

  19. Lin J, Gan CM, Zhang X, et al. A multidimensional analyzes of genes mutated in breast and colorectal cancers. Genome Res 2007;17(9):1304–1318.

    Article  CAS  PubMed  Google Scholar 

  20. Lassere MN, Johnson KR, Boers M, et al. Definitions and validation criteria for biomarkers and surrogate endpoints: development and testing of a quantitative hierarchical levels of evidence schema. J Rheumatol 2007;34(3):607–615.

    PubMed  Google Scholar 

  21. Burczynski ME, Dorner AJ. Transcriptional profiling of peripheral blood cells in clinical pharmacogenomic studies. Pharmacogenomics 2006;7(2):187–202.

    Article  CAS  PubMed  Google Scholar 

  22. Floyd E, McShane TM. Development and use of biomarkers in oncology drug development. Toxicol Pathol 2004;32 Suppl 1:106–115.

    Article  CAS  PubMed  Google Scholar 

  23. Kelloff GJ, Sigman CC. New science-based endpoints to accelerate oncology drug development. Eur J Cancer 2005;41(4):491–501.

    Article  PubMed  Google Scholar 

  24. Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer 2006;6(11):835–845.

    Article  CAS  PubMed  Google Scholar 

  25. Graul AI. Promoting, improving and accelerating the drug development and approval processes. Drug news & perspectives 2007;20(1):45–55.

    CAS  Google Scholar 

  26. Goutsias J, Lee NH. Computational and experimental approaches for modeling gene regulatory networks. Curr Pharm Des 2007;13(14):1415–1436.

    Article  CAS  PubMed  Google Scholar 

  27. Kuick R, Misek DE, Monsma DJ, et al. Discovery of cancer biomarkers through the use of mouse models. Cancer Lett 2007;249(1):40–48.

    Article  CAS  PubMed  Google Scholar 

Challenges to Current Biomarker Development

  1. Logue LJ. Genetic testing coverage and reimbursement: a provider's dilemma. Clin Leadersh Manag Rev 2003;17(6):346–350.

    PubMed  Google Scholar 

  2. Roberts TG, Jr., Chabner BA. Beyond fast track for drug approvals. N Engl J Med 2004;351(5):501–555.

    Article  CAS  PubMed  Google Scholar 

  3. Swanson BN. Delivery of high-quality biomarker assays. Dis Markers 2002;18(2):47–56.

    CAS  PubMed  Google Scholar 

Personalized Molecular Medicine – The Future of Oncology?

  1. Caldwell JS. Cancer cell-based genomic and small molecule screens. Adv Cancer Res 2007;96:145–173.

    Article  CAS  PubMed  Google Scholar 

  2. Watters JW, Roberts CJ. Developing gene expression signatures of pathway deregulation in tumors. Mol Cancer Ther 2006;5(10):2444–2449.

    Article  CAS  PubMed  Google Scholar 

  3. Michor F, Nowak MA, Iwasa Y. Evolution of resistance to cancer therapy. Curr Pharm Des 2006; 12(3):261–271.

    Article  CAS  PubMed  Google Scholar 

A Paradigm Shift – Molecular-Based Indications

  1. Sarkaria JN, Yang L, Grogan PT, et al. Identification of molecular characteristics correlated with glioblastoma sensitivity to EGFR kinase inhibition through use of an intracranial xenograft test panel. Mol Cancer Ther 2007;6(3):1167–1174.

    Article  CAS  PubMed  Google Scholar 

  2. Sequist LV, Bell DW, Lynch TJ, Haber DA. Molecular predictors of response to epidermal growth factor receptor antagonists in non-small-cell lung cancer. J Clin Oncol 2007;25(5):587–595.

    Article  CAS  PubMed  Google Scholar 

  3. Gradishar WJ. Albumin-bound paclitaxel: a next-generation taxane. Expert Opin Pharmacother 2006;7(8):1041–1053.

    Article  CAS  PubMed  Google Scholar 

  4. Gossage L, Madhusudan S. Current status of excision repair cross complementing-group 1 (ERCC1) in cancer. Cancer Treat Rev 2007;33(6):565–577.

    Article  CAS  PubMed  Google Scholar 

  5. Lee JK, Havaleshko DM, Cho H, et al. A strategy for predicting the chemosensitivity of human cancers and its application to drug discovery. Proceedings of the National Academy of Sciences of the United States of America 2007;104(32):13086–13091.

    Google Scholar 

Optimizing the Translational Research Workflow – Development of the Critical Infrastructure

  1. Shtiegman K, Kochupurakkal BS, Zwang Y, et al. Defective ubiquitinylation of EGFR mutants of lung cancer confers prolonged signaling. Oncogene 2007;26(49):6968–6978.

    Google Scholar 

  2. Weinstein IB, Joe AK. Mechanisms of disease: Oncogene addiction—a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 2006;3(8):448–457.

    Article  CAS  PubMed  Google Scholar 

Summary and Future Challenges

  1. Schulenburg A, Ulrich-Pur H, Thurnher D, et al. Neoplastic stem cells: a novel therapeutic target in clinical oncology. Cancer 2006;107(10):2512–2520.

    Article  CAS  PubMed  Google Scholar 

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Correspondence to Craig Paul Webb .

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© 2009 Humana Press, a part of Springer Science+Business Media, LLC

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Webb, C.P., Cherba, D.M. (2009). Systems Biology of Personalized Medicine. In: Krawetz, S. (eds) Bioinformatics for Systems Biology. Humana Press. https://doi.org/10.1007/978-1-59745-440-7_32

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