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Complexity and Information: Cancer as a Multi-Scale Complex Adaptive System

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Physical Sciences and Engineering Advances in Life Sciences and Oncology

Part of the book series: Science Policy Reports ((SCIPOLICY))

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Abstract

Our current understanding of biology and cancer is an implicit model of cellular and organismic regulation with its roots in early biochemical genetics inquiries. The concept that a gene is responsible for a particular protein and can be responsible for a disease was first proposed in 1908 by Archibald Garrod, an English physician (Garrod 1908). Garrod was interested in heritable diseases containing “inborn errors of metabolism.” He suggested (correctly) that alkaptonuria results from a single recessive gene, which causes a deficiency in the enzyme that normally breaks down alkapton. It is now known that alkaptonuria is caused by a defect in homogentisate 1,2-dioxygenase which impairs the degradation of tyrosine (La Du et al. 1958; Zatkova 2011). Beadle and Tatum’s subsequent work demonstrated that single gene mutations could incapacitate specific enzymes, so that neurospora with these mutations had significantly altered physiology—they required an external supply of nutrients to generate something that endogenous enzymes normally produced (Beadle and Tatum 1941).

Life is a relationship among molecules and not a property of any molecule.

—Linus Pauling

Cancer is no more of a disease of cells than a traffic jam is a disease of cars. A lifetime of study of the internal combustion engine would not help anyone to understand our traffic problems. The causes of congestion can be many. A traffic jam is due to failure of the normal relationship between driven cars and their environment and can occur whether they themselves are running normally or not.

—D.W. Smithers, Lancet, March 1962 (Smithers 1962)

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References

  • Ao, P., Galas, D., Hood, L., Zhu, X.: Cancer as robust intrinsic state of endogenous molecular-cellular network shaped by evolution. Med. Hypotheses 70, 678–684 (2008)

    Article  Google Scholar 

  • Aoki, K., Kiyokawa, E., Nakamura, T., Matsuda, M.: Visualization of growth signal transduction cascades in living cells with genetically encoded probes based on Förster resonance energy transfer. Philos. Trans. R. Soc. B 363, 2143–2151 (2008). doi:10.1098/rstb.2008.2267

    Article  Google Scholar 

  • Aoki, K., Takahashi, K., Kunida, K., Yasuda, S., Matsuda, M.: Processive phosphorylation of ERK MAP kinase in mammalian cells. Proc. Natl. Acad. Sci. U. S. A. 108(31), 12675–12680 (2011). doi:10.1073/pnas.1104030108

    Article  ADS  Google Scholar 

  • Aoki, K., Yamada, M., Kaizu, K., Matsuda, M.: A quantitative model of ERK MAP kinase phosphorylation in crowded media. Sci. Rep. 3, 1541 (2013). doi:10.1038/srep01541, 8 pp. [Epub 26 Mar 2013]

    Article  ADS  Google Scholar 

  • Bachmann, J., Raue, A., Schilling, M., Becker, V., Timmer, J., Klingmuller, U.: Predictive mathematical models of cancer signalling pathways. J. Int. Med. 271, 155–165 (2012)

    Article  Google Scholar 

  • Balázsi, G., van Oudenaarden, A., Collins, J.J.: Cellular decision making and biological noise: from microbes to mammals. Cell 144, 910–925 (2011)

    Article  Google Scholar 

  • Bau, D., Marti-Renom, M.A.: Genome structure determination via 3C-based data integration by the Integrative Modeling Platform. Methods 58, 300–306 (2012) [Epub ahead of print, April 13]

    Article  Google Scholar 

  • Beadle, G.W., Tatum, E.L.: Genetic control of biochemical reactions in neurospora. Proc. Natl. Acad. Sci. U. S. A. 27, 499–506 (1941)

    Article  ADS  Google Scholar 

  • Becker, V., Schilling, M., Bachmann, J., Baumann, U., Raue, A., Maiwald, T., Timmer, J., Klingmuller, U.: Covering a broad dynamic range: information processing at the erythropoietin receptor. Science 328, 1404–1408 (2010)

    Article  ADS  Google Scholar 

  • Becker, V., Timmer, J., Klingmuller, U.: Receptor dynamics in signaling. Adv. Exp. Med. Biol. 736, 313–323 (2012)

    Article  Google Scholar 

  • Bertalanffy, L.V.: General System Theory: Foundations, Development, Applications. Penguin, Harmondsworth (1973)

    Google Scholar 

  • Bertolini, F., Marighetti, P., Martin-Padura, I., Mancuso, P., Hu-Lowe, D.D., Shaked, Y., D’Onofrio, A.: Anti-VEGF and beyond: shaping a new generation of anti-angiogenic therapies for cancer. Drug Discov. Today 16, 1052–1060 (2011)

    Article  Google Scholar 

  • Bittig, A.T., Haack, F., Maus, C., Uhrmacher, A.M.: Adapting rule-based model descriptions for simulating in continuous and hybrid space. In: Proceedings of the 9th International Conference on Computational Methods in Systems Biology, pp. 161–170. ACM, Paris (2011)

    Google Scholar 

  • Busch, H., Camacho-Trullio, D., Rogon, Z., Breuhahn, K., Angel, P., Eils, R., Szabowski, A.: Gene network dynamics controlling keratinocyte migration. Mol. Syst. Biol. 4, 199 (2008)

    Article  Google Scholar 

  • Chen, J., Li, Y., Yu, T.-S., McKay, R., Burns, D.K., Kernie, S.G., Parada, L.F.: A restricted cell population propagates glioblastoma growth after chemotherapy. Nature 488, 522–526 (2012). doi:10.1038/nature11287

    Article  ADS  Google Scholar 

  • Chen, X., Chen, J., Gan, S., Guan, H., Zhou, Y., Ouyang, Q., Shi, J.: DNA damage strength modulates a bimodal switch of p53 dynamics for cell-fate control. BMC Biol. 11, 73 (2013). doi:10.1186/1741-7007-11-73

    Article  Google Scholar 

  • Chmielecki, J., Foo, J., Oxnard, G.R., Hutchinson, K., Ohashi, K., Somwar, R., Wang, L., Amato, K.R., Arcila, M., Sos, M.L., Socci, N.D., Viale, A., de Stanchina, E., Ginsberg, M.S., Thomas, R.K., Kris, M.G., Inoue, A., Ladanyi, M., Miller, V.A., Michor, F., Pao, W.: Optimization of dosing for EGFR-mutant non-small cell lung cancer with evolutionary cancer modeling. Sci. Transl. Med. 3(90), 90ra59 (2011). doi:10.1126/scitranslmed.3002356

    Article  Google Scholar 

  • d’Onofrio, A., Gandolfi, A.: Resistance to antitumor chemotherapy due to bounded-noise-induced transitions. Phys. Rev. E 82, 061901 (2010)

    Article  MathSciNet  ADS  Google Scholar 

  • De, S., Michor, F.: DNA replication timing and long-range DNA interactions predict mutational landscapes of cancer genomes. Nat. Biotechnol. 29, 1103–1108 (2011)

    Article  Google Scholar 

  • Deisboeck, T.S., Kresh, J.Y.: Complex Systems Science in Biomedicine. Springer, New York (2006)

    Book  Google Scholar 

  • Driessens, G., Beck, B., Caauwe, A., Simons, B.D., Blanpain, C.: Defining the mode of tumour growth by clonal analysis. Nature 488, 527–530 (2012). doi:10.1038/nature11344

    Article  ADS  Google Scholar 

  • Ewald, R., Himmelspach, J., Jeschke, M., Leye, S., Uhrmacher, A.M.: Flexible experimentation in the modeling and simulation framework JAMES II–implications for computational systems biology. Brief. Bioinform. 11, 290–300 (2010)

    Article  Google Scholar 

  • Fan, H.C., Wang, J., Potanina, A., Quake, S.R.: Whole-genome molecular haplotyping of single cells. Nat. Biotechnol. 29, 51–57 (2011)

    Article  Google Scholar 

  • Fudenberg, G., Getz, G., Meyerson, M., Mirny, L.A.: High order chromatin architecture shapes the landscape of chromosomal alterations in cancer. Nat. Biotechnol. 29, 1109–1113 (2011)

    Article  Google Scholar 

  • Garrod, A.: The Croonian lectures on inborn errors of metabolism. Lancet 172, 1–7 (1908)

    Article  Google Scholar 

  • Gerlinger, M., Rowan, A.J., Horswell, S., Larkin, J., Endesfelder, D., Gronroos, E., Martinez, P., Matthews, N., Stewart, A., Tarpey, P., Varela, I., Phillimore, B., Begum, S., McDonald, N.Q., Butler, A., Jones, D., Raine, K., Latimer, C., Santos, C.R., Nohadani, M., Eklund, A.C., Spencer-Dene, B., Clark, G., Pickering, L., Stamp, G., Gore, M., Szallasi, Z., Downward, J., Futreal, P.A., Swanton, C.: Intratumor heterogeneity and branched evolution revealed by multiregion sequencing. N. Engl. J. Med. 366, 883–892 (2012)

    Article  Google Scholar 

  • Gillies, R.J., Verduzco, D., Gatenby, R.A.: Evolutionary dynamics of carcinogenesis and why targeted therapy does not work. Nat. Rev. Cancer 12, 487–493 (2012)

    Article  Google Scholar 

  • Gobaa, S., Hoehnel, S., Roccio, M., Negro, A., Kobel, S., Lutolf, M.P.: Artificial niche microarrays for probing single stem cell fate in high troughput. Nat. Methods 8, 949–955 (2011)

    Article  Google Scholar 

  • Greaves, M., Maley, C.C.: Clonal evolution in cancer. Nature 481, 306–313 (2012)

    Article  ADS  Google Scholar 

  • Hallatschek, O., Hersen, P., Ramanathan, S., Nelson, D.R.: Genetic drift at expanding frontiers promotes gene segregation. Proc. Natl. Acad. Sci. U. S. A. 104, 19926–19930 (2007)

    Article  ADS  Google Scholar 

  • Huang, S., Ingber, D.E.: A non-genetic basis for cancer progression and metastasis: self-organizing attractors in cell regulatory networks. Breast Dis. 26, 27–54 (2006–2007)

    Google Scholar 

  • Karr, J.R., Sanghvi, J.C., Macklin, D.N., Gutschow, M.V., Jacobs, J.M., Bolival, B., Assad-Garcia, N., Glass, J.I., Covert, M.W.: A whole-cell computational model predicts phenotype from genotype. Cell 150, 389–401 (2012)

    Article  Google Scholar 

  • Kohler, S., Schaller, V., Bausch, A.R.: Collective dynamics of active cytoskeletal networks. PLoS One 6, e23798 (2011)

    Article  ADS  Google Scholar 

  • Kollmann, M., Lovdok, L., Bartholome, K., Timmer, J., Sourjik, V.: Design principles of a bacterial signalling network. Nature 438, 504–507 (2005)

    Article  ADS  Google Scholar 

  • La Du, B.N., Zannoni, V.G., Laster, L., Seegmiller, J.E.: The nature of the defect in tyrosine metabolism in alcaptonuria. J. Biol. Chem. 230, 251–260 (1958)

    Google Scholar 

  • La Porta, C.A., Zapperi, S., Sethna, J.P.: Senescent cells in growing tumors: population dynamics and cancer stem cells. PLoS Comput. Biol. 8, e1002316 (2012)

    Article  MathSciNet  Google Scholar 

  • Laszlo, E.: The Systems View of the World; The Natural Philosophy of the New Developments in the Sciences. G. Braziller, New York (1972)

    Google Scholar 

  • Martens, E.A., Kostadinov, R., Maley, C.C., Hallatschek, O.: Spatial structure increases the waiting time for cancer. New J. Phys. 13, 115014 (2011)

    Article  ADS  Google Scholar 

  • Marti-Renom, M.A., Mirny, L.A.: Bridging the resolution gap in structural modeling of 3D genome organization. PLoS Comput. Biol. 7, e1002125 (2011)

    Article  ADS  Google Scholar 

  • Maus, C., Rybacki, S., Uhrmacher, A.M.: Rule-based multi-level modeling of cell biological systems. BMC Syst. Biol. 5, 166 (2011)

    Article  Google Scholar 

  • Mazemondet, O., Hubner, R., Frahm, J., Koczan, D., Bader, B.M., Weiss, D.G., Uhrmacher, A.M., Frech, M.J., Rolfs, A., Luo, J.: Quantitative and kinetic profile of Wnt/beta-catenin signaling components during human neural progenitor cell differentiation. Cell. Mol. Biol. Lett. 16, 515–538 (2011)

    Article  Google Scholar 

  • Meyerhof, O.: The origin of the reaction of Harden and Young in cell-free alcoholic fermentation. J. Biol. Chem. 157, 105–120 (1945)

    Google Scholar 

  • Meyerhof, O., Junowicz-Kocholaty, R.: The equilibria of isomerase and aldolase, and the problem of the phosphorylation of glyceraldehyde phosphate. J. Biol. Chem. 149, 71 (1943)

    Google Scholar 

  • Meyerhof, O., Oesper, P.: The mechanism of the oxidative reaction in fermentation. J. Biol. Chem. 170, 1 (1947)

    Google Scholar 

  • Munsky, B., Neuert, G., van Oudenaarden, A.: Using gene expression noise to understand gene regulation. Science 336, 183–187 (2012)

    Article  MathSciNet  ADS  Google Scholar 

  • Nakakuki, T., Birtwistle, M.R., Saeki, Y., Yumoto, N., Ide, K., Nagashima, T., Brusch, L., Ogunnaike, B.A., Okada-Hatakeyama, M., Kholodenko, B.M.: Ligand-specific c-Fos expression emerges from the spatiotemporal control of ErbB network dynamics. Cell 141(5), 884–896 (2010). doi:10.1016/j.cell.2010.03.054

    Article  Google Scholar 

  • Okuda, S., Inoue, Y., Eiraku, M., Sasai, Y., Adachi, T.: Reversible network reconnection model for simulating large deformation in dynamic tissue morphogenesis. Biomech. Model. Mechanobiol. 12(4), 627–644 (2013a). doi:10.1007/s10237-012-0430-7

    Article  Google Scholar 

  • Okuda, S., Inoue, Y., Eiraku, M., Sasai, Y., Adachi, T.: Modeling cell proliferation for simulating three-dimensional tissue morphogenesis based on a reversible network reconnection framework. Biomech. Model. Mechanobiol. 12(5), 987–996 (2013b). doi:10.1007/s10237-012-0458-8

    Article  Google Scholar 

  • Pao, W., Chmielecki, J.: Rational, biologically based treatment of EGFR-mutant non-small-cell lung cancer. Nat. Rev. Cancer 10, 760–774 (2010)

    Article  Google Scholar 

  • Prinsen, P., Schiessel, H.: Nucleosome stability and accessibility of its DNA to proteins. Biochimie 92, 1722–1728 (2010)

    Article  Google Scholar 

  • Saiz, L., Vilar, J.M.: Multilevel deconstruction of the In vivo behavior of looped DNA-protein complexes. PLoS One 2, e355 (2007)

    Article  ADS  Google Scholar 

  • Sanyal, A., Bau, D., Marti-Renom, M.A., Dekker, J.: Chromatin globules: a common motif of higher order chromosome structure? Curr. Opin. Cell Biol. 23, 325–331 (2011)

    Article  Google Scholar 

  • Schaller, V., Bausch, A.R.: Materials science: a fresh twist for self-assembly. Nature 481, 268–269 (2012)

    ADS  Google Scholar 

  • Schaller, V., Weber, C., Semmrich, C., Frey, E., Bausch, A.R.: Polar patterns of driven filaments. Nature 467, 73–77 (2010)

    Article  ADS  Google Scholar 

  • Schepers, A.G., Snippert, H.J., Stange, D.E., van den Born, M., van Es, J.H., van de Wetering, M., Clevers, H.: Lineage tracing reveals Lgr5+ stem cell activity in mouse intestinal adenomas. Science 337, 730–735 (2012)

    Article  ADS  Google Scholar 

  • Schwab, E.D., Pienta, K.J.: Cancer as a complex adaptive system. Med. Hypotheses 47, 235–241 (1996)

    Article  Google Scholar 

  • Smithers, D.W.: An attack on cytologism. Lancet 1, 493–499 (1962)

    Article  Google Scholar 

  • Stewart-Orstein, J., Weissman, J.S., El-Samad, H.: Cellular noise regulons underlie fluctuations in Saccharomyces cerevisiae. Mol. Cell 45, 483–493 (2012)

    Article  Google Scholar 

  • Sumino, Y., Nagai, K.H., Shitaka, Y., Tanaka, D., Yoshikawa, K., Chate, H., Oiwa, K.: Large-scale vortex lattice emerging from collectively moving microtubules. Nature 483, 448–452 (2012)

    Article  ADS  Google Scholar 

  • Tambe, D.T., Hardin, C.C., Angelini, T.E., Rajendran, K., Park, C.Y., Serra-Picamal, X., Zhou, E.H., Zaman, M.H., Butler, J.P., Weitz, D.A., Fredburg, J.J., Trepat, X.: Collective cell guidance by cooperative intercellular forces. Nat. Mater. 10, 469–475 (2011)

    Article  ADS  Google Scholar 

  • Trepat, X., Fredberg, J.J.: Plithotaxis and emergent dynamics in collective cellular migration. Trends Cell Biol. 21, 638–646 (2011)

    Article  Google Scholar 

  • Trepat, X., Wasserman, M.R., Angelini, T.E., Millet, E., Weitz, D.A., Butler, J.P., Fredberg, J.J.: Physical forces during collective cell migration. Nat. Phys. 5, 426–430 (2009)

    Article  Google Scholar 

  • Umbarger, M.A., Toro, E., Wright, M.A., Porreca, G.J., Bau, D., Hong, S.H., Fero, M.J., Zhu, L.J., Marti-Renom, M.A., McAdams, H.H., Shapiro, L., Dekker, J., Church, D.M.: The three-dimensional architecture of a bacterial genome and its alteration by genetic perturbation. Mol. Cell 44, 252–264 (2011)

    Article  Google Scholar 

  • Vilar, J.M., Leibler, S.: DNA looping and physical constraints on transcription regulation. J. Mol. Biol. 331, 981–989 (2003)

    Article  Google Scholar 

  • Vilar, J.M., Saiz, L.: Control of gene expression by modulated self-assembly. Nucleic Acids Res. 39, 6854–6863 (2011)

    Article  Google Scholar 

  • Vilar, J.M., Guet, C.C., Leibler, S.: Modeling network dynamics: the lac operon, a case study. J. Cell Biol. 161, 471–476 (2003)

    Article  Google Scholar 

  • Von Bertalanffy, L.: The history and status of general systems theory. In: Klir, G. (ed.) Trends in General Systems Theory, pp. 407–426. Wiley, New York (1972)

    Google Scholar 

  • Wang, G.-W., Zhu, X.-M., Hood, L., Ao, P.: From Phage lambda to human cancer: endogenous molecular-cellular network hypothesis. Quant. Biol. 1(1), 32–49 (2012). doi:10.1007/s40484-013-0007-1

    Article  Google Scholar 

  • Xiong, L., Ma, Y., Tang, L.: Attenuation of transcriptional bursting in mRNA transport. Phys. Biol. 7(1), 016005 (2010). doi:10.1088/1478-3975/7/1/016005

    Article  ADS  Google Scholar 

  • Yu, B., Yang, M., Shi, L., Yao, Y., Jiang, Q., Li, X., Tang, L., Zheng, B.J., Yuen, K., Smith, D.K., Song, E., Huang, J.D.: Explicit hypoxia targeting with tumor suppression by creating an “obligate” anaerobic Salmonella Typhimurium strain. Sci. Rep. 2, 436 (2012). doi:10.1038/srep00436, 10 pp. [EPub 1 Jun 2012]

    ADS  Google Scholar 

  • Zatkova, A.: An update on molecular genetics of Alkaptonuria (AKU). J. Inherit. Metab. Dis. 34, 1127–1136 (2011)

    Article  Google Scholar 

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Authors and Affiliations

  1. Cancer Institute, School of Medicine, Stanford University, Stanford, CA, 94305, USA

    Parag Mallick

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  1. Parag Mallick
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Editors and Affiliations

  1. Institute for Medicine and Engineering, University of Pennsylvania, Philadelphia, Pennsylvania, USA

    Paul Janmey

  2. Bioengineering, University of California, Berkeley, California, USA

    Daniel Fletcher

  3. Department of Chemical and Biomolecular Engineering, JH Physical Sciences-Oncology Center, Institute for NanoBioTechnology, John Hopkins University, Baltimore, Maryland, USA

    Sharon Gerecht

  4. Human Oncology & Pathogenesis Program, Memorial Sloan-Kettering Cancer Center, New York City, New York, USA

    Ross Levine

  5. Cancer Institute, School of Medicine, Stanford University, Stanford, California, USA

    Parag Mallick

  6. Department of Biomedical Engineering, Oregon Health & Science University, Portland, Oregon, USA

    Owen McCarty

  7. Radiation Oncology Edwin L. Steele Lab for Tumor Biology, Harvard Medical School, Charlestown, Massachusetts, USA

    Lance Munn

  8. Department of Biomedical Engineering, Cornell Univesity, Ithaca, New York, USA

    Cynthia Reinhart-King

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Mallick, P. (2016). Complexity and Information: Cancer as a Multi-Scale Complex Adaptive System. In: Janmey, P., et al. Physical Sciences and Engineering Advances in Life Sciences and Oncology. Science Policy Reports. Springer, Cham. https://doi.org/10.1007/978-3-319-17930-8_2

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