Skip to main content
SpringerLink
Log in

The Theory of Biological Robustness and Its Implication in Cancer

  • Conference paper
Systems Biology

Part of the book series: Ernst Schering Research Foundation Workshop ((SCHERING FOUND,volume 61))

Abstract

One of the essential issues in systems biology is to identify fundamental principles that govern living organisms at the system level. In this chapter, I argue that robustness is a fundamental feature of living systems where its relationship with evolution-trade-offs among robustness, fragility, resource demands, and performance-provides a possible framework for how biological systems have evolved and been organized. In addition, diseases can be considered as a manifestation of fragility of the system. In some cases, such as cancer, the disease state establishes its own robustness against therapeutic interventions. Understanding robustness and its intrinsic properties will provide us with a more profound understanding of biological systems, their anomalies, and countermeasures.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  • Agrawal AA (2001) Phenotypic plasticity in the interactions and evolution of species. Science 294:321–326

    Article  PubMed  CAS  Google Scholar 

  • Alon U, Surette MG, Barkai N et al. (1999) Robustness in bacterial chemotaxis. Nature 397:168–171

    Article  PubMed  CAS  Google Scholar 

  • Baisse B, Bouzourene H, Saraga P et al. (2001) Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma. Int J Cancer 93:346–352

    Article  PubMed  CAS  Google Scholar 

  • Bak P, Tang C, Weisenfeld K et al. (1988) Self-organized criticality. Phys Rev A 38:364–374

    Article  PubMed  Google Scholar 

  • Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell’s functional organization. Nat Rev Genet 5:101–113

    Article  PubMed  CAS  Google Scholar 

  • Barkai N, Leibler S (1997) Robustness in simple biochemical networks. Nature 387:913–917

    Article  PubMed  CAS  Google Scholar 

  • Bertalanffy LV (1968) General system theory. George Braziller, New York

    Google Scholar 

  • Bhalla US, Iyengar R (1999) Emergent properties of networks of biological signaling pathways. Science 283:381–387

    Article  PubMed  CAS  Google Scholar 

  • Bingle L, Brown NJ, Lewis CE et al. (2002) The role of tumour-associated macrophages in tumour progression: implications for new anticancer therapies. J Pathol 196:254–265

    Article  PubMed  CAS  Google Scholar 

  • Bissell MJ, Radisky D (2001) Putting tumours in context. Nat Rev Cancer 1:46–54

    Article  PubMed  CAS  Google Scholar 

  • Carlson JM, Doyle J (1999) Highly optimized tolerance: a mechanism for power laws in designed systems. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 60:1412–1427

    PubMed  CAS  Google Scholar 

  • Carlson JM, Doyle J (2002) Complexity and robustness. Proc Natl Acad Sci U S A 99Suppl 1:2538–2545

    Article  PubMed  Google Scholar 

  • Chen KC, Calzone L, Csikasz-Nagy N et al. (2004) Integrative analysis of cell cycle control in budding yeast. Mol Biol Cell 15:3841–3862

    Article  PubMed  CAS  Google Scholar 

  • Csete ME, Doyle J (2004) Bow ties, metabolism and disease. Trends Biotechnol 22:446–450

    Article  PubMed  CAS  Google Scholar 

  • Csete ME, Doyle JC (2002) Reverse engineering of biological complexity. Science 295:1664–1669

    Article  PubMed  CAS  Google Scholar 

  • De Visser J, Hermission J, Wagner GP et al. (2003) Evolution and detection of genetics robustness. Evolution 57:1959–1972

    Article  PubMed  Google Scholar 

  • Dropulic B, Hermankova M, Pitha PM et al. (1996) A conditionally replicating HIV-1 vector interferes with wild-type HIV-1 replication and spread. Proc Natl Acad Sci U S A 93:11103–11108

    Article  PubMed  CAS  Google Scholar 

  • Eldar A, Dorfman R, Weiss D et al. (2002) Robustness of the BMP morphogen gradient in Drosophila embryonic patterning. Nature 419:304–308

    Article  PubMed  CAS  Google Scholar 

  • Ferrell JE Jr (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14:140–148

    Article  PubMed  CAS  Google Scholar 

  • Frigyesi A, Gisselsson D, Mitleman F et al. (2003) Power law distribution of chromosome aberrations in cancer. Cancer Res 63:7094–7097

    PubMed  CAS  Google Scholar 

  • Fujii H, Yoshida M, Gong ZX et al. (2000) Frequent genetic heterogeneity in the clonal evolution of gynecological carcinosarcoma and its influence on phenotypic diversity. Cancer Res 60:114–120

    PubMed  CAS  Google Scholar 

  • Gerhart J, Kirschner M (1997) Cells, embryos, and evolution: toward a cellular and developmental understanding of phenotypic variation and evolutionary adaptability. Blackwell Science, Malden, MA

    Google Scholar 

  • Gonzalez-Garcia I, Sole RV, Costa J et al. (2002) Metapopulation dynamics and spatial heterogeneity in cancer. Proc Natl Acad Sci U S A 99:13085–13089

    Article  PubMed  CAS  Google Scholar 

  • Gorunova L, Dawiskiba S, Andren-Sandberg A et al. (2001) Extensive cytogenetic heterogeneity in a benign retroperitoneal schwannoma. Cancer Genet Cytogenet 127:148–154

    Article  PubMed  CAS  Google Scholar 

  • Gorunova L, Hoglund M, Andren-Sandberg A et al. (1998) Cytogenetic analysis of pancreatic carcinomas: intratumor heterogeneity and nonrandom pattern of chromosome aberrations. Genes Chromosomes Cancer 23:81–99

    Article  PubMed  CAS  Google Scholar 

  • Guelzim N, Bottani S, Bourgine P et al. (2002) Topological and causal structure of the yeast transcriptional regulatory network. Nat Genet 31:60–63

    Article  PubMed  CAS  Google Scholar 

  • Harris AL (2002) Hypoxia-a key regulatory factor in tumour growth. Nat Rev Cancer 2:38–47

    Article  PubMed  CAS  Google Scholar 

  • Hasty J, McMillen D, Collins JJ (2002) Engineered gene circuits. Nature 420:224–230

    Article  PubMed  CAS  Google Scholar 

  • Hochhaus A (2003) Cytogenetic and molecular mechanisms of resistance to imatinib. Semin Hematol 40[2 Suppl 3]:69–79

    PubMed  CAS  Google Scholar 

  • Hochhaus A, Kreil S et al. (2001) Roots of clinical resistance to STI-571 cancer therapy. Science 293:2163

    Article  PubMed  CAS  Google Scholar 

  • Holmgren L, MS O’Reilly, Folkman J et al. (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1:149–153

    Article  PubMed  CAS  Google Scholar 

  • Ideker T, Ozier O, Schwikowski B et al. (2002) Discovering regulatory and signalling circuits in molecular interaction networks. Bioinformatics 18[Suppl 1]: S233–S240

    PubMed  Google Scholar 

  • Ideker T, Thorsson V, Ranish JA et al. (2001) Integrated genomic and proteomic analyses of a systematically perturbed metabolic network. Science 292:929–934

    Article  PubMed  CAS  Google Scholar 

  • Ihmels J, Friedlander G, Bergmann S et al. (2002) Revealing modular organization in the yeast transcriptional network. Nat Genet 31:370–377

    PubMed  CAS  Google Scholar 

  • Ingolia NT (2004) Topology and robustness in the Drosophila segment polarity network. PLoS Biol 2:E123

    Article  PubMed  CAS  Google Scholar 

  • Juliano RL, Ling V (1976) Asurface glycoprotein modulating drug permeability in Chinese hamster ovary cell mutants. Biochim Biophys Acta 455:152–162

    Article  PubMed  CAS  Google Scholar 

  • Kirschner M, Gerhart J (1998) Evolvability. Proc Natl Acad Sci U S A 95:8420–8427

    Article  PubMed  CAS  Google Scholar 

  • Kitano H (2002a) Computational systems biology. Nature 420:206–210

    Article  PubMed  CAS  Google Scholar 

  • Kitano H (2002b) Systems biology: a brief overview. Science 295:1662–1664

    Article  PubMed  CAS  Google Scholar 

  • Kitano H (2003) Cancer robustness: tumour tactics. Nature 426:125

    Article  PubMed  CAS  Google Scholar 

  • Kitano H (2004a) Biological robustness. Nat Rev Genet 5:826–837

    Article  PubMed  CAS  Google Scholar 

  • Kitano H (2004b) Cancer as a robust system: implications for anticancer therapy. Nat Rev Cancer 4:227–235

    Article  PubMed  CAS  Google Scholar 

  • Kitano H, Kimura T, Oda K et al. (2004) Metabolic syndrome and robustness trade-offs. Diabetes 53[Suppl 3]: S1–S10

    Google Scholar 

  • Kitano H, Oda K (2006) Robustness trade-offs and host? Microbial symbiosis in the immune system. Molecular systems biology. Nature Publishing Group and EMBO, Heidelberg

    Google Scholar 

  • Lahav G, Rosenfeld N, Sigal A et al. (2004) Dynamics of the p53-Mdm2 feedback loop in individual cells. Nat Genet 36:147–50

    Article  PubMed  CAS  Google Scholar 

  • Lamport L, Shostak R, Pease M et al. (1982) The Byzantine generals problem. ACM Transa Prog Lang Sys 4:382–401

    Article  Google Scholar 

  • Lengauer C, KW Kinzler, Vogelstein B et al. (1998) Genetic instabilities in human cancers. Nature 396:643–649

    Article  PubMed  CAS  Google Scholar 

  • Li R, Sonik A, Stindl R et al. (2000) Aneuploidy vs. gene mutation hypothesis of cancer: recent study claims mutation but is found to support aneuploidy. Proc Natl Acad Sci U S A 97:3236–3241

    Article  PubMed  CAS  Google Scholar 

  • Little JW, DP Shepley, Wert DW et al. (1999) Robustness of a gene regulatory circuit. EMBO J 18:4299–4307

    Article  PubMed  CAS  Google Scholar 

  • Meir E, G von Dassow, Munro E et al. (2002) Robustness, flexibility, and the role of lateral inhibition in the neurogenic network. Curr Biol 12:778–786

    Article  PubMed  CAS  Google Scholar 

  • Morohashi M, AE Winn, Borisuk MT et al. (2002) Robustness as a measure of plausibility in models of biochemical networks. J Theor Biol 216:19–30

    Article  PubMed  CAS  Google Scholar 

  • Murray C (1995) Tumour dormancy: not so sleepy after all. Nat Med 1:117–118

    Article  PubMed  CAS  Google Scholar 

  • Nooter K, Herweijer H (1991) Multidrug resistance (mdr) genes in human cancer. Br J Cancer 63:663–669

    PubMed  CAS  Google Scholar 

  • Owen MR, HM Byrne, Lewis CE et al. (2004) Mathematical modelling of the use of macrophages as vehicles for drug delivery to hypoxic tumour sites. J Theor Biol 226:377–391

    Article  PubMed  CAS  Google Scholar 

  • Queitsch C, TA Sangster, Lindquist S et al. (2002) Hsp90 as a capacitor of phenotypic variation. Nature 417:618–624

    Article  PubMed  CAS  Google Scholar 

  • Rasnick D (2002) Aneuploidy theory explains tumor formation, the absence of immune surveillance, and the failure of chemotherapy. Cancer Genet Cytogenet 136:66–72

    Article  PubMed  CAS  Google Scholar 

  • Rutherford SL (2003) Between genotype and phenotype: protein chaperones and evolvability. Nat Rev Genet 4:263–274

    Article  PubMed  CAS  Google Scholar 

  • Rutherford SL, Lindquist S (1998) Hsp90 as a capacitor for morphological evolution. Nature 396:336–342

    Article  PubMed  CAS  Google Scholar 

  • Schlichting C, Pigliucci M (1998) Phenotypic evolution: a reaction norm perspective. Sinauer Associates, Inc., Sunderland, MA

    Google Scholar 

  • Schlosser G, Wagner G (eds) (2004) Modularity in development and evolution. The University of Chicago Press, Chicago

    Google Scholar 

  • Sharp FR, Bernaudin M (2004) HIF1 and oxygen sensing in the brain. Nat Rev Neurosci 5:437–448

    Article  PubMed  CAS  Google Scholar 

  • Siegal ML, Bergman A (2002) Waddington’s canalization revisited: developmental stability and evolution. Proc Natl Acad Sci U S A 99:10528–10532

    Article  PubMed  CAS  Google Scholar 

  • Sole RV (2003) Phase transitions in unstable cancer cell populations. Eur Phys J B:117–123

    Google Scholar 

  • Takahashi Y, Nishioka K (1995) Survival without tumor shrinkage: re-evaluation of survival gain by cytostatic effect of chemotherapy. J Natl Cancer Inst 87:1262–1263

    PubMed  CAS  Google Scholar 

  • Tischfield JA, Shao C (2003) Somatic recombination redux. Nat Genet 33:5–6

    Article  PubMed  CAS  Google Scholar 

  • Tsuruo T, Iida H, Tsukagoshi S et al. (1981) Overcoming of vincristine resistance in P388 leukemia in vivo and in vitro through enhanced cytotoxicity of vincristine and vinblastine by verapamil. Cancer Res 41:1967–1972

    PubMed  CAS  Google Scholar 

  • Tyson JJ, Chen K, Novak B (2001) Network dynamics and cell physiology. Nat Rev Mol Cell Biol 2:908–916

    Article  PubMed  CAS  Google Scholar 

  • Uhr JW, RH Scheuermann, Street NE et al. (1997) Cancer dormancy: opportunities for new therapeutic approaches. Nat Med 3:505–509

    Article  PubMed  CAS  Google Scholar 

  • Von Dassow G, Meir E, et al. (2000) The segment polarity network is a robust developmental module. Nature 406:188–192

    Article  Google Scholar 

  • Waddington CH (1957) The strategy of the genes: a discussion of some aspects of theoretical biology. Macmillan, New York

    Google Scholar 

  • Wagner GP, Altenberg L (1996) Complex adaptations and the evolution of evolvability. Evolution 50:967–976

    Article  Google Scholar 

  • Weinberger LS, DV Schaffer, Arkin AP et al. (2003) Theoretical design of a gene therapy to prevent AIDS but not human immunodeficiency virus type 1 infection. J Virol 77:10028–10036

    Article  PubMed  CAS  Google Scholar 

  • Wiener N (1948) Cybernetics: or control and communication in the animal and the machine. MIT Press, Cambridge

    Google Scholar 

  • Yi TM, Huang Y, Simon MI et al. (2000) Robust perfect adaptation in bacterial chemotaxis through integral feedback control. Proc Natl Acad Sci U S A 97:4649–4653

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. The Systems Biology Institute 6A, M31 6-31-15 Jingmuae, Shibuya, Tokyo, 150-0001, Japan

    H. Kitano

Authors
  1. H. Kitano
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Systems Biology, Berlex Biocsciences, 2600 Hilltop Drive, Richmond, CA, 94806, USA

    P. Bringmann

  2. Department of Pathology, Stanford University Medical Center, PAVAMC (154 B), Stanford, CA, 94305-5324, USA

    E. C. Butcher

  3. Berlex Biosciences, 2600 Hilltop Drive, Richmond, CA, 94806, USA

    G. Parry

  4. Genomics & Bioinformatics, Schering AG, Müllerstr. 178, 13342, Berlin, Germany

    B. Weiss

Rights and permissions

Reprints and permissions

Copyright information

© 2007 Springer-Verlag Berlin Heidelberg

About this paper

Cite this paper

Kitano, H. (2007). The Theory of Biological Robustness and Its Implication in Cancer. In: Bringmann, P., Butcher, E.C., Parry, G., Weiss, B. (eds) Systems Biology. Ernst Schering Research Foundation Workshop, vol 61. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-540-31339-7_4

Download citation

Publish with us

Policies and ethics

Search

Navigation