• Papers, Books, and Other Media

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    Edited by Carlo C. Maley and Mel Greaves


    This is the ideal book for anyone contemplating starting a career in, or shifting their career to, studying the dynamics that drive cancer progression and its response to therapy. Topics include the theory and population genetics of cancers, genetic diversity within tumors (intra-tumor heterogeneity), understanding how mutant clones expand in tissues, the role of cancer stem cells in the dynamics of tumors, the evolution of metastasis, and how to improve cancer therapy by addressing the evolution of cancers in response to our interventions. There are also chapters on the patterns of cancer susceptibility in humans due to a mismatch between our modern environment and the environment in which our ancestors evolved, as well as a chapter on the evolution of cancer suppression mechanisms that have evolved in different species, particularly the large long-lived animals like elephants and whales that are better at suppressing cancers than humans.

    This book serves as a primer on the evolutionary and ecological theory of cancer- the framework upon which all the details of cancer may be hung. It is ideal for oncologists and cancer researchers interested in evolutionary theory, and evolutionary biologists and ecologists interested in gaining insights into cancer development and prevention.

    Derivation of genetic biomarkers for cancer risk stratification in Barrett's oesophagus: a prospective cohort study.

    Pan-cancer analysis of intratumor heterogeneity as a prognostic determinant of survival

    Potential Mechanisms for Cancer Resistance in Elephants and Comparative Cellular Response to DNA Damage in Humans.

    Abegglen LM, et al, JAMA. 2015 Nov 3;314(17):1850-60. doi: 10.1001/jama.2015.13134.

    Life history trade-offs in cancer evolution

    Aktipis, CA, et al, Nature Reviews Cancer 13, 883–892 (2013) doi: 10.1038/nrc 3606 Published online 11 November 2013



    Dr. Carlo Maley on Radio Lab: Famous Tumors

    How Nature has Already Beaten Cancer

  • Dr. Maley Bibliography

    PEER REVIEWED PUBLICATIONS: [All inclusive. Numbered. List publications in chronological order (oldest first).]

    1. Maley, C.C., Caswell, H.: Implementing i-state configuration models for populationdynamics - an object-oriented programming approach. Ecological Modelling 68:75-89, 1993.


    2. Maley, C.C.: A model of the effects of dispersal distance on the evolution of virulence in parasites. In Brooks, R., Maes, P. (Eds.) Artificial Life IV, MIT Press, Cambridge, MA, 1994, pp. 152-159.


    3. Maley, C.C.: The computational completeness of Ray's Tierran assembly language. In Langton, C. G. (Ed.) Artificial Life III, Addison-Wesley, Reading, MA, 1994, pp. 503-514.


    4. Maley, C.C.: The coevolution of mutation rates. In Moran, M., Merelo, C. (Eds.) Advances in Artificial Life, Springer-Verlag, Berlin, 1995, pp. 219-233.


    5. Maley, C.: Mutation rates as adaptations. J Theor Biol 186:339-348, 1997.


    6. Maley, C.C.: DNA computation: theory, practice, and prospects. Evol Comput 6:201-229, 1998.


    7. Maley, C.C.: Models of evolutionary ecology and the validation problem. In Adami, C., Belew, R. K., Kitano, H., Taylor, C. E. (Eds.) Artificial Life VI, MIT Press, Cambridge, MA, 1998, pp. 423-427.


    8. Maley, C.C.: Four steps toward open-ended evolution. In Banzhaf, W., Daida, J., Eiben, A. E., Garzon, M. H., Honavar, V., Jakiela, M., Smith, R. E. (Eds.) Genetic and Evolutionary Computation, Morgan Kaufmann Publishers, San Francisco, CA, 1999, pp. 1336-1343.


    9. Maley, C. C.: Comparing causal factors in the diversification of species. InterJournal of Complex Systems BArticle, 2000, p. 241.


    10. Maley, C. C., Forrest, S.: Modeling the role of neutral and selective mutations in cancer in Bedau, M., McCaskill, J., Packard, N., Rasmussen, S. (Eds.) Artificial Life 7, MIT Press, Cambridge, MA, 2000, pp. 395-404.


    11. Maley, C.C., Forrest, S.: Exploring the relationship between neutral and selective mutations in cancer. Artif Life 6:325-345, 2000.


    12. Robeck, H.E., Maley, C.C., Donoghue, M.J.: Taxonomy and temporal diversity patterns. Paleobiology 26:171-187, 2000. Carlo C. Maley 9


    13. Maley, C.C., Tapscott, S.J.: Selective instability: maternal effort and the evolution of gene activation and deactivation rates. Artif Life 9:317-326, 2003.


    14. Maley, C. C., Reid, B. J., Forrest, S.: Cancer prevention strategies that address the evolution of neoplastic cells: Simulating benign cell boosters and selection for chemosensitivity. Cancer Epidemiology, Biomarkers and Prevention, 13:1375-84, 2004.


    15. Maley, C.C., Galipeau, P.C., Li, X., Sanchez, C.A., Paulson, T.G., Reid, B.J.: Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett's esophagus. Cancer Res 64:3414-3427, 2004.


    16. Maley, C.C., Galipeau, P.C., Li, X., Sanchez, C.A., Paulson, T.G., Blount, P.L., Reid, B.J.: The combination of genetic instability and clonal expansion predicts progression to esophageal adenocarcinoma. Cancer Res 64:7629-7633, 2004.


    17. Hornick, J.L., Blount, P.L., Sanchez, C.A., Cowan, D.S., Ayub, K., Maley, C.C., Reid, B.J., Odze, R.D.: Biologic properties of columnar epithelium underneath reepithelialized squamous mucosa in Barrett's esophagus. Am J Surg Pathol 29:372-380, 2005.


    18. Wongsurawat, V.J., Finley, J.C., Galipeau, P.C., Sanchez, C.A., Maley, C.C., Li, X., Blount, P.L., Odze, R.D., Rabinovitch, P.S. and Reid, B.J.: Genetic mechanisms of TP53 loss of heterozygosity in Barrett’s esophagus: Implications for biomarker validation. Cancer Epidemiology, Biomarkers and Prevention, 15:509-516, 2006.


    19. Maley, C.C., Galipeau, P.C., Finley, J.C., Wongsurawat, V.J., Li, X., Sanchez, C.A., Paulson, T.G., Blount, P.L., Risques, R., Rabinovitch, P.S. and Reid, B.J.: Genetic clonal diversity predicts progression to esophageal adenocarcinoma. Nature Genetics, 38:468-473, 2006.


    20. Chao, D.L., Maley, C.C., Wu, X., Farrow, D.C., Galipeau, P.C., Sanchez, C.A., Paulson, T.G., Rabinovitch, P.S., Reid, B.J., Spitz, M.R., and Vaughan, T.L.: Mutagen sensitivity and neoplastic progression in patients with Barrett’s esophagus: A prospective analysis. Cancer Epidemiology, Biomarkers and Prevention, 15:1935-40, 2006. PMCID: PMC2567488


    21. Merlo, L., Pepper, J., Reid, B.J., Maley, C.C.: Cancer as an evolutionary and ecological process. Nature Reviews Cancer, 6:924-35, 2006.


    22. Galipeau, P.C., Li X., Blount, P.L., Maley, C.C., Sanchez, C.A., Odze, R.D., Ayub, K., Rabinovitch, P.S., Vaughan, T.V., Reid, B.J.: NSAIDs modulate CDKN2A, TP53, and DNA content risk for progression to esophageal adenocarcinoma. PLoS Medicine. 4(2):e67, 2007. PMCID: PMC1808095


    23. Srivastava, A., Hornick, J.L., Li, X., Blount, P.L., Sanchez, C.A., Cowan, D.S., Ayub, K., Maley, C.C., Reid, B.J., and Odze R.D.: Extent of low-grade dysplasia Is a risk factor for the development of esophageal adenocarcinoma in Barrett's esophagus. Am. J. Gastro. 102:483-493, 2007.


    24. Lai, L.A., Paulson T.G., Li X., Sanchez C.A., Maley C., Odze R.D., Reid B.J., Rabinovitch, P.S.: Increasing genomic instability during premalignant neoplastic progression revealed through high resolution array-CGH. Genes, Chromosomes and Cancer. 46:532-542, 2007.


    25. Pepper, J., Sprouffske, K., Maley, C.C.: Cell Differentiation Patterns Suppress Somatic Evolution. PLoS Computational Biology, 3:e250, 2007. Highlighted in Nature Online (http://www.nature.com/news/2007/070917/full/news070917-11.html) PMCID: PMC2134960


    26. Chao. D.L., Eck, T., Brash, D., Maley, C.C., Luebeck, E.G.: Pre-neoplastic lesion growth driven by the death of adjacent normal stem cells. PNAS 105:15034-15039, 2008. PMCID: PMC2567488


    27. Li X., Galipeau, P.C., Sanchez, C.A., Blount, P.L., Maley, C.C., Arnaudo, J., Peiffer, D.A., Pokholok, D., Gunderson, K.L., Reid, B.J.: SNP-based Genome-wide Chromosome Copy Carlo C. Maley 10 Change, LOH, and Aneuploidy in Barrett’s Esophagus Neoplastic Progression. Cancer Prevention Research 1:413-423, 2008. PMCID: PMC2882787


    28. Liu, Z., Venkatesh, S.S., Maley, C.C.: Sequence space coverage, entropy of genomes and the potential to detect non-human DNA in human samples. BMC Genomics, 9:509, 2008. PMCID: PMC2628393


    29. Paulson, T.G., Maley, C.C., Chao, D., Li, X., Li, X., Zhang, G., Sanchez, C.A. Odze, R., Vaughan, T., Blount, P., Ayub, K., Reid, B.J.: Copy number alterations in Barrett’s esophagus and esophageal adenocarcinoma. Clinical Cancer Research 15:3305-14, 2009. PMCID: PMC2684570


    30. Pepper, J.W., Findlay, C.S., Kassen, R., Spencer, S.L., and Maley, C.C.: Cancer research meets evolutionary biology. Evolutionary Applications 2:62-70, 2009.


    31. Merlo, L.M.F., Shah, N.A., Li, X., Blount, P., Vaughan, T.L., Reid, B.J., Maley, C.C.: A comprehensive survey of clonal diversity measures in Barrett’s esophagus as biomarkers of progression to esophageal adenocarcinoma. Cancer Prevention Research 3:1388-1397, 2010. PMCID: PMC3004782


    32. Lai, L.A., Kostadinov, R., Barrett, M.T., Peiffer, D.A., Pokholok, D., Odze, R.D., Sanchez, C.A., Maley, C.C., Reid, B.J., Gunderson, K., Rabinovitch, P.S.: Deletion at Fragile Sites is a Common and Early Event in Barrett's Esophagus. Mol Cancer Res. 8:1084-94, 2010. PMCID: PMC3100793


    33. Chen, J., Sprouffske, K., Huang, Q., Maley C.C.: Solving the puzzle of metastasis: The evolution of cell migration in neoplasms. PLoS ONE, 6:e17933, 2011. PMCID: PMC3083389


    34. Aktipis, C.A., Maley, C.C., Pepper, J.W.: Dispersal evolution in neoplasms: The role of disregulated metabolism in the evolution of cell motility. Cancer Prevention Research 5, 266-275 2011. PMCID: PMC3273626


    35. Sprouffske, K., Pepper, J. W. & Maley, C. C.: Accurate reconstruction of the temporal order of mutations in neoplastic progression. Cancer Prevention Research 4:1135-1144, 2011. PMCID: 3131446


    36. Aktipis, C.A., Kwan, V.S.Y., Johnson, K.A., Neuberg, S.L., Maley, C.C.: Overlooking evolution: A systematic analysis of cancer relapse and therapeutic resistance research. PLoS ONE, 6(11):e26100, 2011.


    37. Martens, E.A., Kostadinov, R., Maley, C.C., Hallatschek, O.: Spatial Structure Increases the Waiting Time for Cancer. New Journal of Physics, Focus Issue "Physics of Cancer" 13:115014, 2011. PMCID: PMC3375912


    38. Merlo, L.M.F., Kosoff, R.E., Gardiner, K.L., Maley, C.C.: An in vitro co-culture model of esophageal cells identifies ascorbic acid as a modulator of cell competition. BMC Cancer, 11:461, 2011. PMCID: PMC3213018


    39. Kosoff, R.E., Gardiner, K.L., Merlo, L.M.F., Pavlov, K., Rustgi, A.K., Maley, C.C.: Development and Characterization of an Organotypic Model of Barrett’s Esophagus. Journal of Cellular Physiology. 2012. 227(6): p. 2654-2659. PMCID: PMC3352665


    40. Greaves, M. & Maley, C.C.: Clonal evolution in cancer. Nature. 481:306-313, 2012. PMCID: PMC3367003


    41. Sprouffske, K., Merlo, L.M.F., Gerrish, P.J., Maley, C.C., Sniegowski, P.D.: Cancer in light of experimental evolution. Current Biology, 22:R762-71, 2012. PMCID: PMC3457634


    42. Roche, B., Hochberg, M.E., Caulin, A.F., Maley, C.C., Gatenby, R.A., Missé, D., Thomas, F.: Natural resistance to cancers: a Darwinian hypothesis to explain Peto's paradox. BMC Cancer. 12:387, 2012. PMCID: PMC3488527 Carlo C. Maley 11


    43. Sprouffske, K., Aktipis, C.A., Radich, J.P., Carroll, M., Nedelcu, A.M., Maley, C.C.: An evolutionary explanation for the presence of cancer non-stem cells in neoplasms. Evolutionary Applications, 6: 92-101, 2013. PMCID: PMC3567474


    44. Datta, R.S., Gutteridge, A., Swanton, C., Maley, C.C., Graham, T.A.: Modeling the evolution of genetic instability during tumour progression. Evolutionary Applications 6: 20- 33, 2013. PMCID: PMC3567468


    45. Kostadinov, R.L., Kuhner, M.K., Li, X., Sanchez, C.A., Galipeau, P.C., Paulson, T.G., Sather, C.L., Srivastava, A., Odze, R.D., Blount, P.L., Vaughan, T.L., Reid, B.J., Maley, C.C.: NSAIDs modulate clonal evolution in Barrett’s esophagus. PLoS Genetics, 9:e1003553, 2013. PMCID: PMC3681672


    46. Aktipis, C.A., Boddy, A.M., Gatenby, R.A., Brown, J.S., Maley, C.C.: Life history tradeoffs in cancer evolution. Nature Reviews Cancer, 13:883-892, 2013.


    47. Li, X., Galipeau, P.C., Sanchez, C.A., Paulson, T.P., Arnaudo, J., Liu, K., Sather, C.L., Kostadinov, R.L., Odze, R.D., Kuhner, M.K., Maley, C.C., Self, S.G., Vaughan, T.L., Blount, P.L., Reid, B.J.: Temporal and Spatial Evolution of Somatic Chromosomal Alterations: A Case-Cohort Study of Barrett's Esophagus. Cancer Prevention Research, 7:114-127, 2014.


    48. Alcock, J., Maley, C.C., Aktipis, C.A.: Is eating behavior manipulated by the gastrointestinal microbiota? Evolutionary pressures and potential mechanisms. Bioessays, 36:940-949, 2014 doi: 10.1002/bies.201400071.


    49. Walther, V., Hiley, C.T., Shibata, D., Swanton, C., Turner, P.E., and Maley C.C.: Can oncology recapitulate paleontology? Lessons from species extinctions. Nature Reviews Clinical Oncology, Published online: 17 February 2015 | doi:10.1038/nrclinonc.2015.12


    50. Paguirigan, A.L., Smith, J., Meshinchi, S.,Carroll, M., Maley C.C., Radich, J.P.: Single-cell genotyping demonstrates complex clonal diversity in acute myeloid leukemia. Science Translational Medicine, in press.



    1. Maley, C.C., Reid, B.J.: Barrett's esophagus in Cooper, N.D. (Ed.) Nature Encyclopedia of the Human Genome, Nature Publishing Group, London, UK 1:253-257, 2003.


    2. Maley, C.C. and Reid B.J.: Natural selection in neoplastic progression of Barrett's esophagus. Semin. Cancer Biol. 15:474-83, 2005.


    3. Maley, C.C., Rustgi, A.K.: Barrett's esophagus and its progression to adenocarcinoma. J Natl Compr Canc Netw. 4:367-74, 2006.


    4. Kelloff G.J., Lippman S.M., Dannenberg A.J., Sigman C.C., Pearce H.L., Reid B.J., Szabo E., Jordan V.C., Spitz M.R., Mills G.B., Papadimitrakopoulou V.A., Lotan R., Aggarwal B.B., Bresalier R.S., Kim J., Arun B., Lu K.H., Thomas M.E., Rhodes H.E., Brewer M.A., Follen M., Shin D.M., Parnes H.L., Siegfried J.M., Evans A.A., Blot W.J., Chow W.H., Blount P.L., Maley C.C., Wang K.K., Lam S., Lee J.J., Dubinett S.M., Engstrom P.F., Meyskens F.L. Jr., O'Shaughnessy J., Hawk E.T., Levin B., Nelson W.G., Hong W.K.: Progress in chemoprevention drug development: the promise of molecular biomarkers for prevention of intraepithelial neoplasia and cancer–a plan to move forward. Clinical Cancer Research, 12:3661-3697, 2006. Carlo C. Maley 12


    5. Maley, C.C.: Multistage carcinogenesis in Barrett’s esophagus. Cancer Letters, 245:22-32, 2007.


    6. Maley, C.C.: Open questions in esophageal adenocarcinogenesis. Gut, 56:897-8, 2007. PMCID: PMC1994388


    7. Kelloff, G.J., Sullivan, D.C., Baker, H., Clarke, L.P., Nordstrom, R., Tatum, J.L., Dorfman, G.S., Jacobs, P., Berg, C.D., Pomper, M.G., Birrer, M.J., Tempero, M., Higley, H.R., Petty, B.G., Sigman, C.C., Maley, C., Sharma, P., Wax, A., Ginsberg, G.G., Dannenberg, A.J., Hawk, E.T., Messing, E.M., Grossman, H.B., Harisinghani, M., Bigio, I.J., Griebel, D., Henson, D.E., Fabian, C.J., Ferrara, K., Fantini, S., Schnall, M.D., Zujewski, J.A., Hayes, W., Klein, E.A., DeMarzo, A., Ocak, I., Ketterling, J.A., Tempany, C., Shtern, F., Parnes, H.L., Gomez, J., Srivastava, S., Szabo, E., Lam, S., Seibel, E.J., Massion, P., McLennan, G., Cleary, K., Suh, R., Burt, R.W., Pfeiffer, R.M., Hoffman, J.M., Roy, H.K., Wang, T., Limburg, P.J., El-Deiry, W.S., Papadimitrakopoulou, V., Hittelman, W.N., MacAulay, C., Veltri, R.W., Solomon, D., Jeronimo, J., Richards-Kortum, R., Johnson, K.A., Viner, J.L., Stratton, S.P., Rajadhyaksha, M. and Dhawan, A. Workshop on imaging science development for cancer prevention and preemption. Cancer Biomark 3: 1-33, 2007.


    8. Merlo, L.M.F. and Maley, C.C.: The role of genetic diversity in cancer. J Clin Invest 120, 401-3, 2010. PMCID: PMC2810093


    9. Aktipis, C.A., Maley, C.C., and Neuberg, S.L.: Psychological barriers to evolutionary thinking in medicine. Evolution and Medicine Review (February 24, 2010). http://evmedreview.com/?p=231


    10. Cairo, M.S., Jordan, C., Maley, C.C., Chao, C., Melnick, A., Armstrong, S.A., Shlomchik, W., Molldrem, J., Ferrone, S., Tycko, B., Mackall, C., Zitvogel, L., June, C.H.: NCI 1st International Workshop on The Biology, Prevention, and Treatment of Relapse After Allogeneic Hematopoietic Stem Cell Transplantation: Report from the Committee on the Biological Considerations of Hematological Relapse Following Allogeneic Stem Cell Transplantation Unrelated to Graft Versus Tumor Effects: State of the Science. Biology of Blood and Marrow Transplantation 16,709-728, 2010.


    11. Pavlov, K. and Maley, C.C.: New models of neoplastic progression in Barrett's oesophagus. Biochem Soc Trans 38, 331-6, 2010. PMCID: PMC2866622


    12. Odze, R.D. and Maley, C.C.: Neoplasia without dysplasia: lessons from Barrett esophagus and other tubal gut neoplasms. Arch Pathol Lab Med 134 (6), 896-906, 2010.


    13. Caulin, A.F. and Maley, C.C.: Peto's Paradox: Evolution's Prescription for Cancer Prevention. Trends in Evolution and Ecology, 26:175-82, 2011. PMCID: PMC3060950


    14. Reid, B.J., Kostadinov, R. and Maley, C.C.:New Strategies in Barrett's Esophagus: Integrating clonal evolutionary theory with clinical management. Clin Can Res, 17:3512-9, 2011. PMCID: PMC3119197


    15. Aktipis, C. A. & Maley, C. C.: The Self-ish Cell: Cancer's emerging evolutionary paradigm. Evolution and Medicine Review, 764, 2011. Books and Chapters


    16. Maley, C.C.: Artificial Biology: Computer as Petri Dish in Enrado, P., Keppler, K. (Ed.) Explorations in Artificial Life, AI Expert Presents, San Francisco, CA, 1995, pp. 36-39.


    17. Maley, C.C.: Evolutionary computation for evolutionary theory in Ghosh, A., Tsutsui, S. (Eds.) Theory and Application of Evolutionary Computation: Recent Trends, SpringerVerlag, Berlin, 2003, pp. 441-460. Carlo C. Maley 13


    18. Maley, C.C.: DNA computing and its frontiers in Sienko, T., Rambidi, N., Conrad, M. (Eds.) Molecular Computing, MIT Press, Cambridge, MA, 2003, pp. 153-189.


    19. Maley, C. C.: Biological computation: From DNA to cells in Morkoc, H. (Ed.) Advanced Semiconductor and Organic Nano-techniques III. Academic Press, New York, NY 2005, pp. 371-405.


    20. Merlo, L.M.F., Wang, L., Pepper J.W., Rabinovitch, P.S., Maley, C.C.: Polyploidy, Aneuploidy and the Evolution of Cancer. In: Poon, R.Y.C., ed. Polyploidization and Cancer. Austin/New York: Landes Bioscience, Inc. and Springer Science+Business Media, 2010, pp. 1-13.


    21. Sprouffske, K. and Maley, C.C.: Cooperation and Cancer. In: Cancer Genome and Tumor Microenvironment. Thomas-Tikhonenko, A. (Ed.), 2010, pp. 471-85.


    22. Maley, C.C., Lewis, W., and Reid, B.J.: Has cancer sculpted the genome? Modeling linkage and the role of tetraploidy in neoplastic progression. In Diesboeck, T. and Stamatakos, G., eds. Multiscale Cancer Modeling. Chapman & Hall, 2010, pp. 45-66.


    23. Maley, C.C., E. Szabo, and B.J. Reid: Somatic Evolution in Neoplastic Progression and Cancer Prevention, in Pre-Invasive Disease: Pathogenesis and Clinical Management, R.C. Fitzgerald, Editor, 2011, p. 111-127. Other Publications


    24. Maley, C.C.: Cancer: The Evolutionary Legacy by M. Greaves. Heredity. 88:219, 2002.