Abstract
Cancer treatment is a fragmented and varied process, as “cancer” is really hundreds of different diseases. The “hallmarks of cancer” were proposed by Hanahan and Weinberg in 2000 and gave a framework for viewing cancer as a single disease - one where cells have acquired ten properties that are common to almost all cancers, allowing them to grow uncontrollably and ravage the body. We used a cellular automata model of tumour growth paired with lattice Boltzmann methods modelling oxygen flow to simulate combination drugs targeted at knocking out pairs of hallmarks. We found that knocking out some pairs of cancer-enabling hallmarks did not prevent tumour formation, while other pairs significantly prevent cancer from growing beyond a few cells (p=0.0004 using Wilcoxon signed-rank adjusted with Bonferroni for multiple comparisons). This is not what would be expected from models of knocking out the hallmarks individually, as many pairs did not have an additive effect but either had no effect or a multiplicative one. We propose that targeting certain pairs of cancer hallmarks, specifically cancer’s ability to induce blood vessel development paired with another cancer hallmark, could prove an effective cancer treatment option.
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References
Abbott, R., Forrest, S., Pienta, K.: Simulating the hallmarks of cancer. Artificial Life 4(12), 34–617 (2006)
Anderson, A.R.A., Rejniak, K.A., Gerlee, P., Quaranta, V.: Modelling of Cancer Growth, Evolution and Invasion: Bridging Scales and Models. Mathematical Modelling of Natural Phenomena 2(3), 1–29 (2008), http://www.mmnp-journal.org/10.1051/mmnp:2007001
Anderson, A.R.A., Quaranta, V.: Integrative mathematical oncology. Nature Reviews Cancer 8(3), 227–234 (2008), http://www.ncbi.nlm.nih.gov/pubmed/18273038
Anderson, A.R.A., Weaver, A.M., Cummings, P.T., Quaranta, V.: Tumor morphology and phenotypic evolution driven by selective pressure from the microenvironment. Cell 127(5), 905–915 (2006), http://www.ncbi.nlm.nih.gov/pubmed/17129778
Basanta, D., Ribba, B., Watkin, E., You, B., Deutsch, A.: Computational analysis of the influence of the microenvironment on carcinogenesis. Mathematical Biosciences 229(1), 22–29 (2011), http://www.sciencedirect.com/science/article/pii/S0025556410001616
Bello, L., Lucini, V., Costa, F., Pluderi, M., Giussani, C., Acerbi, F., Carrabba, G., Pannacci, M., Caronzolo, D., Grosso, S., et al.: Combinatorial administration of molecules that simultaneously inhibit angiogenesis and invasion leads to increased therapeutic efficacy in mouse models of malignant glioma. Clinical Cancer Research 10(13), 4527–4537 (2004)
Bellomo, N., De Angelis, E.: Selected topics in cancer modeling: genesis, evolution, immune competition, and therapy. Springer (2008)
Bentley, K., Bates, P., Gerhardt, H.: Artificial life as cancer research: Embodied agent modelling of blood vessel growth in tumours. In: Proceedings of Artifical Life XI (2008)
Ebos, J.M.L., Lee, C.R., Cruz-Munoz, W., Bjarnason, G.A., Christensen, J.G., Kerbel, R.S.: Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15(3), 232–239 (2009), http://www.ncbi.nlm.nih.gov/pubmed/19249681
Gerlee, P., Anderson, A.R.A.: An evolutionary hybrid cellular automaton model of solid tumour growth. Journal of Theoretical Biology 246(4), 583–603 (2007)
Gerlee, P., Anderson, A.R.A.: A hybrid cellular automaton model of clonal evolution in cancer: The emergence of the glycolytic phenotype. Journal of Theoretical Biology 250, 705–722 (2008)
Gerlee, P., Anderson, A.R.A.: Evolution of cell motility in an individual-based model of tumour growth. Journal of Theoretical Biology 259(1), 67–83 (2009)
Gevertz, J.L., Gillies, G.T., Torquato, S.: Simulating tumor growth in confined heterogeneous environments. Physical Biology 5(3) (2008), http://www.ncbi.nlm.nih.gov/pubmed/18824788
Hanahan, D., Weinberg, R.: The hallmarks of cancer. Cell 100(1), 57–70 (2000)
Hanahan, D., Weinberg, R.: Hallmarks of cancer: the next generation. Cell 144(5), 646–674 (2011)
Henderson, E., Samaha, R.: Evidence that drugs in multiple combinations have materially advanced the treatment of human malignancies. Cancer Research 29(12), 2272–2280 (1969)
Hirata, Y., Bruchovsky, N., Aihara, K.: Development of a mathematical model that predicts the outcome of hormone therapy for prostate cancer. Journal of Theoretical Biology 264(2), 517–527 (2010), http://www.ncbi.nlm.nih.gov/pubmed/20176032
Kam, Y., Rejniak, K.A., Anderson, A.R.A.: Cellular modeling of cancer invasion: integration of in silico and in vitro approaches. Journal of Cellular Physiology 227(2), 431–438 (2012), http://www.ncbi.nlm.nih.gov/pubmed/21465465
Lloyd, B.A., Szczerba, D., Rudin, M., Székely, G.: A computational framework for modelling solid tumour growth. Philosophical transactions, Series A, Mathematical, physical, and engineering sciences 366(1879), 3301–3318 (2008), http://www.ncbi.nlm.nih.gov/pubmed/18593664
Macklin, P., Edgerton, M.E., Thompson, A., Cristini, V.: Patient-calibrated agent-based modelling of ductal carcinoma in situ (DCIS) I: Model formulation and analysis. Journal of Theoretical Biology 301, 122–140 (2011)
Maley, C.C., Forrest, S.: Modelling the role of neutral and selective mutations in cancer. In: Artificial Life VII: Proceedings of the Seventh International Conference on Artificial Life, pp. 395–404 (2000)
Ramis-Conde, I., Chaplain, M.A.J., Anderson, A.R.: Mathematical modelling of cancer cell invasion of tissue. Mathematical and Computer Modelling 47(5-6), 533–545 (2008), http://linkinghub.elsevier.com/retrieve/pii/S0895717707001823
Rejniak, K.A., Anderson, A.R.A.: State of the art in computational modelling of cancer. Mathematical Medicine and Biology 29(1), 1–2 (2012), http://www.ncbi.nlm.nih.gov/pubmed/22200587
Rejniak, K.A., Anderson, A.R.: Hybrid models of tumor growth. Wiley Interdisciplinary Reviews: Systems Biology and Medicine 3(1), 115–125 (2011)
Ribba, B., Alarcón, T., Marron, K., Maini, P.K., Agur, Z.: The use of hybrid cellular automaton models for improving cancer therapy. In: Sloot, P.M.A., Chopard, B., Hoekstra, A.G. (eds.) ACRI 2004. LNCS, vol. 3305, pp. 444–453. Springer, Heidelberg (2004)
Santos, J., Monteagudo, Á.: Study of cancer hallmarks relevance using a cellular automaton tumor growth model. In: Coello, C.A.C., Cutello, V., Deb, K., Forrest, S., Nicosia, G., Pavone, M. (eds.) PPSN 2012, Part I. LNCS, vol. 7491, pp. 489–499. Springer, Heidelberg (2012)
Sener, S., Fremgen, A., Menck, H., Winchester, D.: Pancreatic cancer: A report of treatment and survival trends for 100,313 patients diagnosed from 1985–1995, using the national cancer database. Journal of the American College of Surgeons 189(1), 1–7 (1999)
Shrestha, S., Joldes, G.R., Wittek, A., Miller, K.: Cellular automata coupled with steady-state nutrient solution permit simulation of large-scale growth of tumours. International Journal for Numerical Methods in Biomedical Engineering 29, 542–559 (2013)
Spencer, S., Berryman, M., Garcia, J., Abbott, D.: An ordinary differential equation model for the multistep transformation to cancer. Journal of Theoretical Biology 231, 515–524 (2004)
StatCan: Leading causes of death, by sex. Statistics Canada (2009)
Sun, X., Zhang, L., Tan, H., Bao, J., Strouthos, C., Zhou, X.: Multi-scale agent-based brain cancer modeling and prediction of TKI treatment response: Incorporating EGFR signaling pathway and angiogenesis. BMC Bioinformatics 13(1), 218 (2012), http://www.biomedcentral.com/1471-2105/13/218
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Butler, J., Mackay, F., Denniston, C., Daley, M. (2014). Simulating Cancer Growth Using Cellular Automata to Detect Combination Drug Targets. In: Ibarra, O., Kari, L., Kopecki, S. (eds) Unconventional Computation and Natural Computation. UCNC 2014. Lecture Notes in Computer Science(), vol 8553. Springer, Cham. https://doi.org/10.1007/978-3-319-08123-6_6
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DOI: https://doi.org/10.1007/978-3-319-08123-6_6
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