Hostname: page-component-7d684dbfc8-hsbzg Total loading time: 0 Render date: 2023-09-25T04:17:23.333Z Has data issue: false Feature Flags: { "corePageComponentGetUserInfoFromSharedSession": true, "coreDisableEcommerce": false, "coreDisableSocialShare": false, "coreDisableEcommerceForArticlePurchase": false, "coreDisableEcommerceForBookPurchase": false, "coreDisableEcommerceForElementPurchase": false, "coreUseNewShare": true, "useRatesEcommerce": true } hasContentIssue false

What and How Do Cancer Systems Biologists Explain?

Published online by Cambridge University Press:  01 January 2022


In this article, we argue, first, that there are very different research projects that fall under the heading of “systems biology of cancer.” While they share some general features, they differ in their aims and theoretical commitments. Second, we argue that some explanations in systems biology of cancer are concerned with properties of signaling networks (such as robustness or fragility) and how they may play an important causal role in patterns of vulnerability to cancer. Further, some systems biological explanations are compelling illustrations of how “top-down” and “bottom-up” approaches to the same phenomena may be integrated.

Copyright © The Philosophy of Science Association

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)


The article was jointly developed by both authors and the thesis commonly shared. Anya Plutynski was mainly responsible for writing sec. 2, and Marta Bertolaso, for writing secs. 1 and 4.


Alon, Uri. 2007. “Network Motifs: Theory and Experimental Approaches.” Nature Reviews Genetics 8 (6): 450–61..10.1038/nrg2102CrossRefGoogle ScholarPubMed
Amit, Ido, Wides, Ron, and Yarden, Yosef. 2007. “Evolvable Signaling Networks of Receptor Tyrosine Kinases: Relevance of Robustness to Malignancy and to Cancer Therapy.” Molecular Systems Biology 3 (1): 114..10.1038/msb4100195CrossRefGoogle ScholarPubMed
Ao, Ping, Galas, David, Hood, Leroy, and Zhu, Xiaomei. 2008. “Cancer as Robust Intrinsic State of Endogenous Molecular-Cellular Network Shaped by Evolution.” Medical Hypotheses 70 (3): 678–84..CrossRefGoogle ScholarPubMed
Bansal, Mukesh, Belcastro, Vincenzo, Ambesi-Impiombato, Alberto, and Bernardo, Diego Di. 2007. “How to Infer Gene Networks from Expression Profiles.” Molecular Systems Biology 3 (1): 78.10.1038/msb4100120CrossRefGoogle ScholarPubMed
Barillot, Emmanuel, Calzone, Laurence, Hupe, Philippe, Vert, Jean-Philippe, and Zinovyev, Andrei. 2012. Computational Systems Biology of Cancer. Boca Raton, FL: CRC.10.1201/b12677CrossRefGoogle Scholar
Bo, Valeria, and Tucker, Allan. 2015. “Integrating Gene Regulatory Networks to Identify Cancer-Specific Genes.” In Proceedings of the American Medical Informatics Association Joint Summits on Translational Science Proceedings, 2125. Bethesda, MD: AMIA.Google Scholar
Brigandt, Ingo, Green, Sara, and O’Malley, Maureen A.. 2017. “Systems Biology and Mechanistic Explanation.” In The Routledge Handbook of Mechanisms and Mechanical Philosophy, ed. Glennan, Stuart and Illari, Phyllis. London: Routledge.Google Scholar
Bruggeman, Frank J., and Westerhoff, Hans V.. 2007. “The Nature of Systems Biology.” Trends in Microbiology 15 (1): 4550..CrossRefGoogle ScholarPubMed
Craver, Carl F. 2016. “The Explanatory Power of Network Models.” Philosophy of Science 83 (5): 698709..10.1086/687856CrossRefGoogle Scholar
Deisboeck, Thomas S., Wang, Zhihui, Macklin, Paul, and Cristini, Vittorio. 2011. “Multiscale Cancer Modeling.” Annual Review of Biomedical Engineering 13:127–55.10.1146/annurev-bioeng-071910-124729CrossRefGoogle ScholarPubMed
Dvorak, Harold F. 1986. “Tumors: Wounds That Do Not Heal.” New England Journal of Medicine 315 (26): 1650–59..Google Scholar
Dvorak, Harold F. 2015. “Tumors: Wounds That Do Not Heal; Redux.” Cancer Immunology Research 3 (1): 111..10.1158/2326-6066.CIR-14-0209CrossRefGoogle Scholar
Ekstrand, A. J., James, C. D., Cavenee, W. K., Seliger, B., Pettersson, R. F., and Collins, V. P.. 1991. “Genes for Epidermal Growth Factor Receptor, Transforming Growth Factor α, and Epidermal Growth Factor and Their Expression in Human Gliomas in Vivo.Cancer Research 51:2164–72.Google ScholarPubMed
Fagan, Melinda Bonnie. 2012. “Waddington Redux: Models and Explanation in Stem Cell and Systems Biology.” Biology and Philosophy 27 (2): 179213..CrossRefGoogle Scholar
Fogarty, M. P., Kessler, J. D., and Wechsler-Reya, R. J.. 2005. “Morphing into Cancer: The Role of Developmental Signaling Pathways in Brain Tumor Formation.” Journal of Neurobiology 64 (4): 458–75..10.1002/neu.20166CrossRefGoogle ScholarPubMed
Green, Sara, Fagan, Melinda, and Jaeger, Johannes. 2015. “Explanatory Integration Challenges in Evolutionary Systems Biology.” Biological Theory 10 (1): 1835..10.1007/s13752-014-0185-8CrossRefGoogle Scholar
Huang, Sui, Ernberg, Ingemar, and Kauffman, Stuart. 2009. “Cancer Attractors: A Systems View of Tumors from a Gene Network Dynamics and Developmental Perspective.” Seminars in Cell and Developmental Biology 20 (7): 869–76..10.1016/j.semcdb.2009.07.003CrossRefGoogle ScholarPubMed
Huang, Sui, and Ingber, Donald E.. 2007. “A Non-genetic Basis for Cancer Progression and Metastasis: Self-Organizing Attractors in Cell Regulatory Networks.” Breast Disease 26 (1): 2754..CrossRefGoogle Scholar
Huneman, Philippe. 2017. “Outlines of a Theory of Structural Explanations.” Philosophical Studies 175 (3): 665702..CrossRefGoogle Scholar
Ingber, Donald E. 2008. “Can Cancer Be Reversed by Engineering the Tumor Microenvironment?Seminars in Cancer Biology 18:356–64.CrossRefGoogle ScholarPubMed
Laforge, Bertrand, Guez, David, Martinez, Michael, and Kupiec, Jean-Jacques. 2005. “Modeling Embryogenesis and Cancer: An Approach Based on an Equilibrium between the Autostabilization of Stochastic Gene Expression and the Interdependence of Cells for Proliferation.” Progress in Biophysics and Molecular Biology 89 (1): 93120..CrossRefGoogle Scholar
Levine, Michael, and Davidson, Eric H.. 2005. “Gene Regulatory Networks for Development.” Proceedings of the National Academy of the Sciences of the USA 102 (14): 4936–42..Google ScholarPubMed
National Research Council. 2009. A New Biology for the 21st Century. Washington, DC: National Academies.Google Scholar
Nazarieh, Maryam, Wiese, Andreas, Will, Thorsten, Hamed, Mohamed, and Helms, Volkhard. 2016. “Identification of Key Player Genes in Gene Regulatory Networks.” BMC Systems Biology 10 (1): 88.CrossRefGoogle ScholarPubMed
O’Malley, Maureen A., Brigandt, Ingo, Love, Alan C., Crawford, John W., Gilbert, Jack A., Knight, Rob, Mitchell, Sandra D., and Rohwer, Forest. 2014. “Multilevel Research Strategies and Biological Systems.” Philosophy of Science 81 (5): 811–28..10.1086/677889CrossRefGoogle Scholar
O’Malley, Maureen A., and Dupré, John. 2005. “Fundamental Issues in Systems Biology.” BioEssays 27 (12): 1270–76..Google ScholarPubMed
Sadeghi, Mehdi, Ranjbar, Bijan, Ganjalikhany, Mohamad Reza, Khan, Faiz M., Schmitz, Ulf, Wolkenhauer, Olaf, and Gupta, Shailendra K.. 2016. “MicroRNA and Transcription Factor Gene Regulatory Network Analysis Reveals Key Regulatory Elements Associated with Prostate Cancer Progression.” PLoS One 11 (12): e0168760.10.1371/journal.pone.0168760CrossRefGoogle ScholarPubMed
Slamon, D. J., Clark, G. M., Wong, S. G., Levin, W. J., Ullrich, A., and McGuire, W. L.. 1987. “Human Breast Cancer: Correlation of Relapse and Survival with Amplification of the HER-2/neu Oncogene.” Science 235:177–82.CrossRefGoogle ScholarPubMed
Udyavar, Akshata R., Wooten, David J., Hoeksema, Megan, Bansal, Mukesh, Califano, Andrea, Estrada, Lourdes, Schnell, Santiago, Irish, Jonathan M., Massion, Pierre P., and Quaranta, Vito. 2017. “Novel Hybrid Phenotype Revealed in Small Cell Lung Cancer by a Transcription Factor Network Model That Can Explain Tumor Heterogeneity.” Cancer Research 77 (5): 1063–74..10.1158/0008-5472.CAN-16-1467CrossRefGoogle ScholarPubMed
Van Laere, Steven, Dirix, Luc, and Vermeulen, Peter. 2016. “Molecular Profiles to Biology and Pathways: A Systems Biology Approach.” Chinese Journal of Cancer 35 (1): 53.10.1186/s40880-016-0112-4CrossRefGoogle ScholarPubMed
Wagner, Andreas. 2005. “Distributed Robustness versus Redundancy as Causes of Mutational Robustness.” Bioessays 27 (2): 176–88..10.1002/bies.20170CrossRefGoogle ScholarPubMed
Weinberg, Robert. 2013. The Biology of Cancer. New York: Garland Science.CrossRefGoogle Scholar
Weinberg, Robert 2014. “Coming Full Circle: From Endless Complexity to Simplicity and Back Again.” Cell 157 (1): 267–71..CrossRefGoogle Scholar
Yarden, Yosef, and Pines, Gur. 2012. “The ERBB Network: At Last, Cancer Therapy Meets Systems Biology.” Nature Reviews Cancer 12 (8): 553–63..CrossRefGoogle ScholarPubMed