What does physics have to do with cancer?

Nature Reviews Cancer

Volumn 11, Issue 9, 2011, Pages 657-670

  Michor, Franziska ^a   Liphardt, Jan ^b   Ferrari, Mauro ^c   Widom, Jonathan ^d  

^a HARVARD SCHOOL OF PUBLIC HEALTH   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

^c HOUSTON METHODIST RESEARCH INSTITUTE   (United States)

^d NORTHWESTERN UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYCLIN DEPENDENT KINASE INHIBITOR 2A; EPIDERMAL GROWTH FACTOR RECEPTOR; NEUROFIBROMIN; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE;

CANCER DIAGNOSIS; CANCER RESEARCH; CARCINOGENESIS; CHROMATIN; CHROMOSOME STRUCTURE; DISEASE COURSE; DNA SEQUENCE; GENE DOSAGE; GENE MAPPING; GENE MUTATION; GENETIC ASSOCIATION; GENOTYPE; HUMAN; NONHUMAN; NUCLEOSOME; PHYSICS; PRIORITY JOURNAL; REVIEW;

BIOMECHANICS; BIOMEDICAL RESEARCH; BIOPHYSICAL PHENOMENA; HUMANS; NEOPLASMS; NEOPLASTIC PROCESSES; NONLINEAR DYNAMICS; PHYSICS;

EID: 80052038990     PISSN: 1474175X     EISSN: 14741768     Source Type: Journal    
DOI: 10.1038/nrc3092     Document Type: Review

References (146)

1. Paget, S. The distribution of secondary growths in cancer of the breast. Lancet 1, 571-573 (1889).
2. Boehm, T., Folkman, J., Browder, T. & O'Reilly, M.S. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390, 404-407 (1997). (Pubitemid 28027321)
3. Nowell, P.C. The clonal evolution of tumor cell populations. Science 194, 23-28 (1976).
4. Armitage, P. & Doll, R. A two-stage theory of carcinogenesis in relation to the age distribution of human cancer. Br. J.Cancer 11, 161-169 (1957).
5. Fisher, J.C. Multiple-mutation theory of carcinogenesis. Nature 181, 651-652 (1958).
6. [Author unknown.] The Edwin Smith Surgical Papyrus, Vault RB, NY Acad. Med. Rare Book Room, New York (c1,600bce).
7. Butcher, D.T., Alliston, T. & Weaver, V.M. A tense situation: forcing tumour progression. Nature Rev. Cancer 9, 108-122 (2009).
8. Levental, K.R. etal. Matrix crosslinking forces tumor progression by enhancing integrin signaling. Cell 139, 891-906 (2009).
9. Schedin, P. & Keely, P.J. Mammary gland ECM remodeling, stiffness, and mechanosignaling in normal development and tumor progression. Cold Spring Harb. Perspect. Biol. 3, a003228 (2011).
10. Montell, D.J. Morphogenetic cell movements: diversity from modular mechanical properties. Science 322, 1502-1505 (2008).
11. Mariappan, Y.K., Glaser, K.J. & Ehman, R.L. Magnetic resonance elastography: a review. Clin. Anat. 23, 497-511 (2010).
12. Hansma, P. etal. The tissue diagnostic instrument. Rev. Sci. Instrum. 80, 054303 (2009).
13. Krieg, M. etal. Tensile forces govern germ-layer organization in zebrafish. Nature Cell Biol. 10, 429-436 (2008).
14. Salaita, K. etal. Restriction of receptor movement alters cellular response: physical force sensing by EphA2. Science 327, 1380-1385 (2010).
15. Taylor, J.E. Structure of singularities in soap-bubble-like and soap-film-like minimal surfaces. Ann. Math. 103, 489-539 (1976).
16. Hayashi, T. & Carthew, R.W. Surface mechanics mediate pattern formation in the developing retina. Nature 431, 647-652 (2004). (Pubitemid 39382604)
17. Kafer, J., Hayashi, T., Maree, A.F., Carthew, R.W. & Graner, F. Cell adhesion and cortex contractility determine cell patterning in the Drosophila retina. Proc. Natl Acad. Sci. USA 104, 18549-18554 (2007). (Pubitemid 350210734)
18. Hilgenfeldt, S., Erisken, S. & Carthew, R.W. Physical modeling of cell geometric order in an epithelial tissue. Proc. Natl Acad. Sci. USA 105, 907-911 (2008). (Pubitemid 351282054)
19. Acar, M., Pando, B.F., Arnold, F.H., Elowitz, M.B. & van Oudenaarden, A. A general mechanism for network-dosage compensation in gene circuits. Science 329, 1656-1660 (2010).
20. Sprinzak, D. et al. Cis-interactions between Notch and Delta generate mutually exclusive signalling states. Nature 465, 86-90 (2010).
21. Cairns, J. Mutation selection and the natural history of cancer. Nature 255, 197-200 (1975).
22. Heppner, G.H. & Miller, F.R. The cellular basis of tumor progression. Int. Rev. Cytol. 177, 1-56 (1998). (Pubitemid 128716720)
23. Crespi, B. & Summers, K. Evolutionary biology of cancer. Trends Ecol. Evol. 20, 545-552 (2005). (Pubitemid 41323711)
24. Michor, F., Iwasa, Y. & Nowak, M.A. Dynamics of cancer progression. Nature Rev. Cancer 4, 197-205 (2004). (Pubitemid 38337499)
25. Merlo, L.M., Pepper, J.W., Reid, B.J. & Maley, C.C. Cancer as an evolutionary and ecological process. Nature Rev. Cancer 6, 924-935 (2006). (Pubitemid 44862677)
26. Brash, D.E., Zhang, W., Grossman, D. & Takeuchi, S. Colonization of adjacent stem cell compartments by mutant keratinocytes. Semin. Cancer Biol. 15, 97-102 (2005). (Pubitemid 40126240)
27. Maley, C.C. et al. Selectively advantageous mutations and hitchhikers in neoplasms: p16 lesions are selected in Barrett's esophagus. Cancer Res. 64, 3414-3427 (2004). (Pubitemid 38657913)
28. Keller, L. Levels of Selection in Evolution. (Princeton Univ. Press, 1999).
29. Weinstein, B.S. & Ciszek, D. The reserve-capacity hypothesis: evolutionary origins and modern implications of the trade-off between tumor-suppression and tissue-repair. Exp. Gerontol. 37, 615-627 (2002). (Pubitemid 34224107)
30. Knudson, A.G. Jr. Mutation and cancer: statistical study of retinoblastoma. Proc. Natl Acad. Sci. USA 68, 820-823 (1971).
31. Haeno, H., Levine, R.L., Gilliland, D.G. & Michor, F. A progenitor cell origin of myeloid malignancies. Proc. Natl Acad. Sci. USA 106, 16616-16621 (2009).
32. Tomlinson, I.P. Novelli, M.R. & Bodmer, W.F. The mutation rate and cancer. Proc. Natl Acad. Sci. USA 93, 14800-14803 (1996). (Pubitemid 26419049)
33. Desper, R. et al. Inferring tree models for oncogenesis from comparative genome hybridization data. J.Comput. Biol. 6, 37-51 (1999). (Pubitemid 29166360)
34. Goldie, J.H. & Coldman, A.J. Quantitative model for multiple levels of drug resistance in clinical tumors. Cancer Treat. Rep. 67, 923-931 (1983). (Pubitemid 14231384)
35. Coldman, A.J. & Murray, J.M. Optimal control for a stochastic model of cancer chemotherapy. Math. Biosci. 168, 187-200 (2000).
36. Michor, F. et al. Dynamics of chronic myeloid leukaemia. Nature 435, 1267-1270 (2005). (Pubitemid 40943094)
37. Coldman, A.J. & Goldie, J.H. A stochastic model for the origin and treatment of tumors containing drug-resistant cells. Bull. Math. Biol. 48, 279-292 (1986). (Pubitemid 17005602)
38. Skipper, H.E. The forty-year-old mutation theory of Luria and Delbruck and its pertinence to cancer chemotherapy. Adv. Cancer Res. 40, 331-363 (1983).
39. Iwasa, Y., Michor, F. & Nowak, M.A. Evolutionary dynamics of escape from biomedical intervention. Proc. Biol. Sci. 270, 2573-2578 (2003). (Pubitemid 38082944)
40. Komarova, N.L. & Wodarz, D. Drug resistance in cancer: principles of emergence and prevention. Proc. Natl Acad. Sci. USA 102, 9714-9719 (2005). (Pubitemid 40981746)
41. Durrett, R. & Moseley, S. Evolution of resistance and progression to disease during clonal expansion of cancer. Theor. Popul. Biol. 77, 42-48 (2010).
42. Harnevo, L.E. & Agur, Z. The dynamics of gene amplification described as a multitype compartmental model and as a branching process. Math. Biosci. 103, 115-138 (1991).
43. Goldie, J.H. & Coldman, A.J. The genetic origin of drug resistance in neoplasms: implications for systemic therapy. Cancer Res. 44, 3643-3653 (1984). (Pubitemid 14041569)
44. Day, R.S. Treatment sequencing, asymmetry, and uncertainty: protocol strategies for combination chemotherapy. Cancer Res. 46, 3876-3885 (1986). (Pubitemid 16075878)
45. Citron, M.L. et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J.Clin. Oncol. 21, 1431-1439 (2003). (Pubitemid 46594092)
46. Komarova, N.L., Katouli, A.A. & Wodarz, D. Combination of two but not three current targeted drugs can improve therapy of chronic myeloid leukemia. PLoS ONE 4, e4423 (2009).
47. Foo, J. & Michor, F. Evolution of resistance to anti-cancer therapy during general dosing schedules. J.Theor. Biol. 263, 179-188 (2010).
48. Knudson, A.G. Two genetic hits (more or less) to cancer. Nature Rev. Cancer 1, 157-162 (2001). (Pubitemid 33741891)
49. Nordling, C.O. A new theory on cancer-inducing mechanism. Br. J.Cancer 7, 68-72 (1953).
50. Varmus, H. The new era in cancer research. Science 312, 1162-1165 (2006). (Pubitemid 43801131)
51. Weir, B., Zhao, X. & Meyerson, M. Somatic alterations in the human cancer genome. Cancer Cell 6, 433-438 (2004). (Pubitemid 39469978)
52. Futreal, P.A. et al. A census of human cancer genes. Nature Rev. Cancer 4, 177-183 (2004). (Pubitemid 38337497)
53. The Cancer Genome Atlas Research Network. Comprehensive genomic characterization defines human glioblastoma genes and core pathways. Nature 455, 1061-1068 (2008).
54. Beroukhim, R. et al. The landscape of somatic copy-number alteration across human cancers. Nature 463, 899-905 (2010).
55. Hanahan, D. & Weinberg, R.A. The hallmarks of cancer. Cell 100, 57-70 (2000). (Pubitemid 30046295)
56. Feinberg, A.P., Ohlsson, R. & Henikoff, S. The epigenetic progenitor origin of human cancer. Nature Rev. Genet. 7, 21-33 (2006). (Pubitemid 41828945)
57. Hastings, P.J., Lupski, J.R., Rosenberg, S.M. & Ira, G. Mechanisms of change in gene copy number. Nature Rev. Genet. 10, 551-564 (2009).
58. Stratton, M.R., Campbell, P.J. & Futreal, P.A. The cancer genome. Nature 458, 719-724 (2009).
59. Wang, G. & Vasquez, K.M. Naturally occurring H-DNA-forming sequences are mutagenic in mammalian cells. Proc. Natl Acad. Sci. USA 101, 13448-13453 (2004). (Pubitemid 39238423)
60. Wang, G., Christensen, L.A. & Vasquez, K.M. Z.-DNA-forming sequences generate large-scale deletions in mammalian cells. Proc. Natl Acad. Sci. USA 103, 2677-2682 (2006).
61. Zhao, J., Bacolla, A., Wang, G. & Vasquez, K.M. Non-B DNA structure-induced genetic instability and evolution. Cell. Mol. Life Sci. 67, 43-62 (2010).
62. Huppert, J.L. Structure, location and interactions of G.quadruplexes. FEBS J. 277, 3452-3458 (2010).
63. Lipps, H.J. & Rhodes, D. G.quadruplex structures: invivo evidence and function. Trends Cell Biol. 19, 414-422 (2009).
64. Maizels, N. Dynamic roles for G4 DNA in the biology of eukaryotic cells. Nature Struct. Mol. Biol. 13, 1055-1059 (2006). (Pubitemid 44885914)
65. Sun, D. & Hurley, L.H. Biochemical techniques for the characterization of G-quadruplex structures: EMSA, DMS footprinting, and DNA polymerase stop assay. Methods Mol. Biol. 608, 65-79 (2010).
66. De, S. & Michor, F. DNA secondary structures and epigenetic determinants of cancer genome evolution. Nature Struct. Mol. Biol. 3Jul 2011 (doi:10.1038/nsmb.2089).
67. Kruisselbrink, E. et al. Mutagenic capacity of endogenous G4 DNA underlies genome instability in FANCJ-defective C.elegans. Curr. Biol. 18, 900-905 (2008).
68. Pontier, D.B., Kruisselbrink, E., Guryev, V. & Tijsterman, M. Isolation of deletion alleles by G4 DNA-induced mutagenesis. Nature Methods 6, 655-657 (2009).
69. Boan, F. & Gomez-Marquez, J. Invitro recombination mediated by G-quadruplexes. Chembiochem 11, 331-334 (2010).
70. Attolini, C.S. et al. A mathematical framework to determine the temporal sequence of somatic genetic events in cancer. Proc. Natl Acad. Sci. USA 107, 17604-17609 (2010).
71. Hartl, D.L. & Clark, A.G. Principles of Population Genetics. 4th edn (Sinauer Associates, 2007).
72. Fearon, E.R. & Vogelstein, B. A genetic model for colorectal tumorigenesis. Cell 61, 759-767 (1990).
73. Zhu, Y. et al. Early inactivation of p53 tumor suppressor gene cooperating with NF1 loss induces malignant astrocytoma. Cancer Cell 8, 119-130 (2005). (Pubitemid 41132741)
74. Abdel-Wahab, O. et al. Genetic analysis of transforming events that convert chronic myeloproliferative neoplasms to leukemias. Cancer Res. 70, 447-452 (2010).
75. Beroukhim, R. et al. Assessing the significance of chromosomal aberrations in cancer: methodology and application to glioma. Proc. Natl Acad. Sci. USA 104, 20007-20012 (2007).
76. Bachoo, R.M. et al. Epidermal growth factor receptor and Ink4a/Arf: convergent mechanisms governing terminal differentiation and transformation along the neural stem cell to astrocyte axis. Cancer Cell 1, 269-277 (2002). (Pubitemid 41039151)
77. Zhu, H. et al. Oncogenic EGFR signaling cooperates with loss of tumor suppressor gene functions in gliomagenesis. Proc. Natl Acad. Sci. USA 106, 2712-2716 (2009).
78. Segal, E. et al. A genomic code for nucleosome positioning. Nature 442, 772-778 (2006). (Pubitemid 44258903)
79. Kornberg, R.D. & Lorch, Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285-294 (1999). (Pubitemid 29380564)
80. Richmond, T.J. & Davey, C.A. The structure of DNA in the nucleosome core. Nature 423, 145-150 (2003). (Pubitemid 36569532)
81. Field, Y. et al. Gene expression divergence in yeast is coupled to evolution of DNA-encoded nucleosome organization. Nature Genet. 41, 438-445 (2009).
82. Field, Y. et al. Distinct modes of regulation by chromatin encoded through nucleosome positioning signals. PLoS Comput. Biol. 4, e1000216 (2008).
83. Eaton, M.L., Galani, K., Kang, S., Bell, S.P. & MacAlpine, D.M. Conserved nucleosome positioning defines replication origins. Genes Dev. 24, 748-753 (2010).
84. Getun, I.V., Wu, Z.K., Khalil, A.M. & Bois, P.R. J. Nucleosome occupancy landscape and dynamics at mouse recombination hotspots. EMBO Rep. 11, 555-560 (2010).
85. Sasaki, S. et al. Chromatin-associated periodicity in genetic variation downstream of transcriptional start sites. Science 323, 401-404 (2009).
86. Lanzer, M., Wertheimer, S.P., de Bruin, D. & Ravetch, J.V. Chromatin structure determines the sites of chromosome breakages in Plasmodium falciparum. Nucleic Acids Res. 22, 3099-3103 (1994). (Pubitemid 24260641)
87. Wang, G.P., Ciuffi, A., Leipzig, J., Berry, C.C. & Bushman, F.D. HIV integration site selection: analysis by massively parallel pyrosequencing reveals association with epigenetic modifications. Genome Res. 17, 1186-1194 (2007). (Pubitemid 47204862)
88. Pryciak, P.M. & Varmus, H.E. Nucleosomes, DNA-binding proteins, and DNA sequence modulate retroviral integration target site selection. Cell 69, 769-780 (1992).
89. Gangadharan, S., Mularoni, L., Fain-Thornton, J., Wheelan, S.J. & Craig, N.L. DNA transposon Hermes inserts into DNA in nucleosome-free regions invivo. Proc. Natl Acad. Sci. USA 107, 21966-21972 (2010).
90. Palomera-Sanchez, Z. & Zurita, M. Open, repair and close again: chromatin dynamics and the response to UV-induced DNA damage. DNA Repair 10, 119-125 (2010).
91. Bucceri, A., Kapitza, K. & Thoma, F. Rapid accessibility of nucleosomal DNA in yeast on a second time scale. EMBO J. 25, 3123-3132 (2006). (Pubitemid 44106763)
92. Prendergast, J.G. D. et al. Chromatin structure and evolution in the human genome. BMC Evol. Biol. 7, 72 (2007).
93. Widom, J. Role of DNA sequence in nucleosome stability and dynamics. Q.Rev. Biophys. 34, 269-324 (2001). (Pubitemid 34121497)
94. Cloutier, T.E. & Widom, J. Spontaneous sharp bending of double-stranded DNA. Mol. Cell 14, 355-362 (2004). (Pubitemid 38591406)
95. Segal, E. & Widom, J. Poly(dA:dT) tracts: major determinants of nucleosome organization. Curr. Opin. Struct. Biol. 19, 65-71 (2009).
96. Thåström, A., Bingham, L.M. & Widom, J. Nucleosomal locations of dominant DNA sequence motifs for histone-DNA interactions and nucleosome positioning. J.Mol. Biol. 338, 695-709 (2004). (Pubitemid 38507415)
97. Morozov, A. et al. Using DNA mechanics to predict invitro nucleosome positions and formation energies. Nucleic Acids Res. 37, 4707-4722 (2009).
98. Tolstorukov, M.Y., Colasanti, A.V., McCandlish, D.M., Olson, W.K. & Zhurkin, V.B. A novel roll-and-slide mechanism of DNA folding in chromatin: implications for nucleosome positioning. J.Mol. Biol. 371, 725-738 (2007). (Pubitemid 47087819)
99. Geggier, S. & Vologodskii, A. Sequence dependence of DNA bending rigidity. Proc. Natl Acad. Sci. USA 107, 15421-15426 (2010).
100. Wiggins, P.A. et al. High flexibility of DNA on short length scales probed by atomic force microscopy. Nature Nanotech. 1, 137-141 (2006).
101. Lavery, R. et al. A systematic molecular dynamics study of nearest-neighbor effects on base pair and base pair step conformations and fluctuations in B-DNA. Nucleic Acids Res. 38, 299-313 (2010).
102. Zakrzewska, K., Bouvier, B., Michon, A., Blanchet, C. & Lavery, R. Protein-DNA binding specificity: a grid-enabled computational approach applied to single and multiple protein assemblies. Phys. Chem. Chem. Phys. 11, 10712-10721 (2009).
103. Lankas, F. et al. On the parameterization of rigid base and basepair models of DNA from molecular dynamics simulations. Phys. Chem. Chem. Phys. 11, 10565-10588 (2009).
104. Kaplan, N. et al. The DNA-encoded nucleosome organization of a eukaryotic genome. Nature 458, 362-366 (2009).
105. Fraser, R.M., Allan, J. & Simmen, M.W. Insilico approaches reveal the potential for DNA sequence-dependent histone octamer affinity to influence chromatin structure invivo. J.Mol. Biol. 364, 582-598 (2006). (Pubitemid 44755317)
106. Chevereau, G., Palmeira, L., Thermes, C., Arneodo, A. & Vaillant, C. Thermodynamics of intragenic nucleosome ordering. Phys. Rev. Lett. 103, 188103 (2009).
107. Schwab, D.J., Bruinsma, R.F., Rudnick, J. & Widom, J. Nucleosome switches. Phys. Rev. Lett. 100, 228105 (2008).
108. Segal, E. & Widom, J. From DNA sequence to transcriptional behaviour: a quantitative approach. Nature Rev. Genet. 10, 443-456 (2009).
109. Raveh-Sadka, T., Levo, M. & Segal, E. Incorporating nucleosomes into thermodynamic models of transcription regulation. Genome Res. 19, 1480-1496 (2009).
110. Segal, E. & Widom, J. What controls nucleosome positions? Trends Genet. 25, 335-343 (2009).
111. Strukov, Y.G. & Belmont, A.S. Mitotic chromosome structure: reproducibility of folding and symmetry between sister chromatids. Biophys. J. 96, 1617-1628 (2009).
112. Subramanian, H. et al. Optical methodology for detecting histologically unapparent nanoscale consequences of genetic alterations in biological cells. Proc. Natl Acad. Sci. USA 105, 20118-20123 (2008).
113. Subramanian, H. et al. Nanoscale cellular changes in field carcinogenesis detected by partial wave spectroscopy. Cancer Res. 69, 5357-5363 (2009).
114. Damania, D. et al. Role of cytoskeleton in controlling the disorder strength of cellular nanoscale architecture. Biophys. J. 99, 989-996 (2010).
115. Kim, J.S., Pradhan, P., Backman, V. & Szleifer, I. The influence of chromosome density variations on the increase in nuclear disorder strength in carcinogenesis. Phys. Biol. 8, 015004 (2011).
116. Hudson, T.J. et al. International network of cancer genome projects. Nature 464, 993-998 (2010).
117. Fidler, I.J. & Kripke, M.L. Metastasis results from preexisting variant cells within a malignant tumor. Science 197, 893-895 (1977). (Pubitemid 8168759)
118. Navin, N. et al. Inferring tumor progression from genomic heterogeneity. Genome Res. 20, 68-80 (2010).
119. Berger, M.F. et al. The genomic complexity of primary human prostate cancer. Nature 470, 214-220 (2011).
120. Beerenwinkel, N. et al. Genetic progression and the waiting time to cancer. PLoS Comput. Biol. 3, e225 (2007).
121. Yachida, S. et al. Distant metastasis occurs late during the genetic evolution of pancreatic cancer. Nature 467, 1114-1117 (2010).
122. Campbell, P.J. et al. The patterns and dynamics of genomic instability in metastatic pancreatic cancer. Nature 467, 1109-1113 (2010).
123. Huh, D. & Paulsson, J. Non-genetic heterogeneity from stochastic partitioning at cell division. Nature Genet. 43, 95-100 (2011).
124. van Engeland, M. Derks, S., Smits, K.M., Meijer, G.A. & Herman, J.G. Colorectal cancer epigenetics: complex simplicity. J.Clin. Oncol. 29, 1382-1391 (2011).
125. Hondermarck, H. Breast cancer: when proteomics challenges biological complexity. Mol. Cell. Proteomics 2, 281-291 (2003).
126. Fidler, I.J. & Hart, I.R. Biological diversity in metastatic neoplasms: origins and implications. Science 217, 998-1003 (1982). (Pubitemid 12059094)
127. Copeland, N.G. & Jenkins, N.A. Deciphering the genetic landscape of cancer-from genes to pathways. Trends Genet. 25, 455-462 (2009).
128. Wooster, R. & Bachman, K.E. Catalogue, cause, complexity and cure; the many uses of cancer genome sequence. Curr. Opin. Genet. Dev. 20, 336-341 (2010).
129. Auffray, C., Imbeaud, S., Roux-Rouquie, M. & Hood, L. From functional genomics to systems biology: concepts and practices. C.R.Biol. 326, 879-892 (2003). (Pubitemid 38016443)
130. Liu, E.T., Kuznetsov, V.A. & Miller, L.D. In the pursuit of complexity: systems medicine in cancer biology. Cancer Cell 9, 245-247 (2006).
131. Check Hayden, E. Cancer complexity slows quest for cure. Nature 455, 148 (2008).
132. Sjoblom, T. et al. The consensus coding sequences of human breast and colorectal cancers. Science 314, 268-274 (2006). (Pubitemid 44571966)
133. Ferrari, M. Frontiers in cancer nanomedicine: directing mass transport through biological barriers. Trends Biotechnol. 28, 181-188 (2010).
134. Moore, N.M., Kuhn, N.Z., Hanlon, S.E., Lee, J.S. & Nagahara, L.A. De-convoluting cancer's complexity: using a 'physical sciences lens' to provide a different (clearer) perspective of cancer. Phys. Biol. 8, 010302 (2011).
135. Bearer, E.L. et al. Multiparameter computational modeling of tumor invasion. Cancer Res. 69, 4493-4501 (2009).
136. Cristini, V. & Lowengrub, J. Multiscale Modeling Of Cancer: An Integrated Experimental And Mathematical Modeling Approach (Cambridge Univ. Press, 2010).
137. Kim, P. et al. Invivo wide-area cellular imaging by side-view endomicroscopy. Nature Methods 7, 303-305 (2010).
138. Ananta, J.S. et al. Geometrical confinement of gadolinium-based contrast agents in nanoporous particles enhances T1 contrast. Nature Nanotechnol. 5, 815-821 (2010).
139. Tasciotti, E. et al. Mesoporous silicon particles as a multistage delivery system for imaging and therapeutic applications. Nature Nanotechnol. 3, 151-157 (2008). (Pubitemid 351355132)
140. Tanaka, T. et al. Sustained small interfering RNA delivery by mesoporous silicon particles. Cancer Res. 70, 3687-3696 (2010).
141. Ferrari, M. Vectoring siRNA therapeutics into the clinic. Nature Rev. Clin. Oncol. 7, 485-486 (2010).
142. Decuzzi, P. & Ferrari, M. Design maps for nanoparticles targeting the diseased microvasculature. Biomaterials 29, 377-384 (2008). (Pubitemid 350081047)
143. Decuzzi, P. & Ferrari, M. The adhesive strength of non-spherical particles mediated by specific interactions. Biomaterials 27, 5307-5314 (2006). (Pubitemid 44080296)
144. Gentile, F., Ferrari, M. & Decuzzi, P. The transport of nanoparticles in blood vessels: the effect of vessel permeability and blood rheology. Ann. Biomed. Eng. 36, 254-261 (2008).
145. Serda, R.E. et al. Logic-embedded vectors for intracellular partitioning, endosomal escape, and exocytosis of nanoparticles. Small 6, 2691-2700 (2010).
146. Nickerson, J. A., Krockmalnic, G., Wan, K. M. & Penman, S. The nuclear matrix revealed by eluting chromatin from a cross-linked nucleus. Proc. Natl Acad. Sci. USA 94, 4446-4450 (1997). (Pubitemid 27194261)