Genetic and epigenetic heterogeneity in cancer: The ultimate challenge for drug therapy

Current Drug Targets

Volumn 11, Issue 10, 2010, Pages 1304-1316

  Heng, H H ^a   Liu, G ^a   Stevens, J B ^a   Bremer, S W ^a   Ye, K J ^b   Ye, C J ^a  

^a WAYNE STATE UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b SeeDNA Biotech Inc   (Canada)

Author keywords

Cancer evolutionary mechanism; Drug resistance; Genetic and epigenetic heterogeneity; Genome theory; Genomic instability; Molecular targeting; Non clonal chromosome aberrations (NCCAs)

Indexed keywords

DNA VACCINE; HISTONE DEACETYLASE INHIBITOR;

ARTICLE; CANCER CELL; CHROMOSOMAL INSTABILITY; DNA METHYLATION; EPIGENETICS; GENE EXPRESSION; GENETIC HETEROGENEITY; GENOMIC INSTABILITY; HUMAN; METABOLIC REGULATION; MISMATCH REPAIR; NEOPLASM; NONHUMAN;

EID: 77957984508     PISSN: 13894501     EISSN: None     Source Type: Journal    
DOI: 10.2174/1389450111007011304     Document Type: Article

References (140)

1. Abdullah-Sayani A, Bueno-de-Mesquita JM, van de Vijver MJ. Technology Insight: tuning into the genetic orchestra using microarrays-limitations of DNA microarrays in clinical practice. Nat Clin Pract Oncol 2002; 3: 501-16.
2. Greenman C, Stephens P, Smith R, et al. Patterns of somatic mutation in human cancer genome. Nature 2007; 446: 153-8.
3. Wood LD, Parsons DW, Jones S, et al. The genomic landscapes of human breast and colorectal cancers. Science 2007; 318: 1108-13.
4. Jones S, Zhang X, Parsons DW, et al. Core signaling pathways in human pancreatic cancers revealed by global genomic analyses. Science 2008; 321: 1801-6.
5. Parsons DW, Jones S, Zhang X, et al. An integrated genomic analysis of human glioblastoma multiforme. Science 2008; 321: 1807-12.
6. Hahn WC, Weinberg RA. Modeling the molecular circuitry of cancer. Nat Rev Cancer 2002; 2: 331-41.
7. Vogelstein B, Kinzler KW. Cancer genes and the pathways they control. Nat Med 2004; 10:789-99.
8. Rebbaa A. Targeting senescence pathways to reverse drug resistance in cancer. Cancer Lett 2005; 219: 1-13.
9. Rubio-Viqueira, B, Hidalgo M. Targeting mTOR for cancer treatment. Adv Exp Med Biol 2006; 587: 309-27.
10. Weinstein IB, Joe AK. Mechanisms of disease: Oncogene addiction-a rationale for molecular targeting in cancer therapy. Nat Clin Pract Oncol 2006; 3: 448-57.
11. Marcus R. Use of 90Y-ibritumomab tiuxetan in non-Hodgkin's lymphoma. Semin Oncol 2005; 32: S36-43.
12. Sakamoto J, Annapragada A, Decuzzi P, et al. Antibiological barrier nanovector technology for cancer applications. Expert Opin Drug Deliv 2007; 4: 359-69.
13. Petrelli A, Giordano S. From single-to multi-target drugs in cancer therapy: when aspecificity becomes an advantage. Curr Med Chem 2008; 15: 422-32.
14. Rini BI, Atkins, MB. Resistance to targeted therapy in renal-cell carcinoma. Lancet Oncol 2009; 10: 992-1000.
15. Folini M, Gandellini P, Zaffaroni N. Targeting the telosome: therapeutic implications. Biochim Biophys Acta 2009; 1792: 309-16.
16. Harley CB. Telomerase and cancer therapeutics. Nat Rev Cancer 2008; 8: 167-79.
17. Zhou J, Giannakakou P. Targeting microtubules for cancer chemotherapy. Curr Med Chem Anticancer Agents 2005; 5: 65-71.
18. Miglarese MR, Carlson RO. Development of new cancer therapeutic agents targeting mitosis. Expert Opin Investig Drugs. 2006; 15: 1411-25.
19. Stevens JB, Liu G, Bremer SW, et al. Mitotic cell death by chromosome fragmentation. Cancer Res 2007; 67: 7686-94.
20. Reed JC. Drug insight: cancer therapy strategies based on restoration of endogenous cell death mechanisms. Nat Clin Pract Oncol 2006; 3: 388-98.
21. Dias N, Bailly C. Drugs targeting mitochondrial functions to control tumor cell growth. Biochem Pharmacol 2005; 70: 1-12.
22. Jones RG, Thompson CB. Tumor suppressors and cell metabolism: a recipe for cancer growth. Genes Dev 2009; 23: 537-48.
23. Sheng H, Niu B, Sun H. Metabolic targeting of cancers: from molecular mechanisms to therapeutic strategies. Curr Med Chem 2009; 16: 1561-87.
24. Ishii Y, Waxman S, Germain D. Targeting the ubiquitin-proteasome pathway in cancer therapy. Anticancer Agents Med Chem 2007; 7: 359-65.
25. Yan Y, Kitagaki J, Wang H, et al. Targeting the ubiquitin-proteasome system for cancer therapy. Cancer Sci 2009; 100: 24-8.
26. Arcangeli A, Crociani O, Lastraioli E, et al. Targeting ion channels in cancer: a novel frontier in antineoplastic therapy. Curr Med Chem 2009; 16: 66-93.
27. Aggarwal BB, Vijayalekshmi RV, Sung B. Targeting inflammatory pathways for prevention and therapy of cancer: short-term friend, long-term foe. Clin Cancer Res 2009; 15: 425-30.
28. Bissell MJ, Kenny PA, Radisky DC. Microenvironmental regulators of tissue structure and function also regulate tumor induction and progression: the role of extracellular matrix and its degrading enzymes. Cold Spring Harb Symp Quant Biol 2005; 70: 343-56.
29. Colotta F, Allavena P, Sica A, et al. Cancer-related inflammation, the seventh hallmark of cancer: links to genetic instability. Carcinogenesis 2009; 30: 1073-81.
30. Zaidi SK, Young DW, Javed A, et al. Nuclear microenvironments in biological control and cancer. Nat Rev Cancer 2007; 7: 454-63.
31. Meads MB, Gatenby RA, Dalton WS. Environment-mediated drug resistance: a major contributor to minimal residual disease. Nat Rev Cancer 2009; 9: 665-74.
32. Hirte HW. Novel developments in angiogenesis cancer therapy. Curr Oncol 2009; 16: 50-4.
33. Moser C, Lang SA, Stoeltzing O. Heat-shock protein 90 (Hsp90) as a molecular target for therapy of gastrointestinal cancer. Anticancer Res 2009; 29: 2031-42.
34. Higgins CF. Multiple molecular mechanisms for multidrug resistance transporters. Nature 2007; 446: 749-57.
35. Dean M, Fojo T, Bates S. Tumour stem cells and drug resistance. Nat Rev Cancer 2005; 5: 275-84.
36. Zhou BB, Zhang H, Damelin M, et al. Tumour-initiating cells: challenges and opportunities for anticancer drug discovery. Nat Rev Drug Discov 2009; 8: 806-23.
37. Schatton T, Frank NY, Frank MH. Identification and targeting of cancer stem cells. Bioessays 2009; 31: 1038-49.
38. Kater AP, van Oers MH, Kipps TJ. Cellular immune therapy for chronic lymphocytic leukemia. Blood 2007; 110: 2811-8.
39. Cocco C, Pistoia V, Airoldi I. New perspectives for melanoma immunotherapy: role of IL-12. Curr Mol Med 2009; 9: 459-69.
40. Hernández P, Solé X, Valls J, et al. Integrative analysis of a cancer somatic mutome. Mol Cancer 2007; 6:13.
41. Allan JM, Travis LB. Mechanisms of therapy-related carcinogenesis. Nat Rev Cancer 2005; 5: 943-55.
42. Fojo T, Grady C. How much is life worth: cetuximab, non-small cell lung cancer, and the $440 billion question. J Natl Cancer Inst 2009; 101:1044-8.
43. Heng HH. Cancer genome sequencing: the challenges ahead. Bioessays 2007a; 29: 783-794.
44. Heppner GH. Tumor heterogeneity. Cancer Res 1984; 44: 2259-65.
45. Heppner GH, Miller FR. The cellular basis of tumor progression. Int Rev Cytol 1998; 177: 1-56.
46. Heng HH, Stevens JB, Liu G, et al. Imaging genome abnormalities in cancer research. Cell Chromosome 2004a; 3: 1.
47. Heng HH, Liu G, Bremer S, et al. Clonal and non-clonal chromosome aberrations and genome variation and aberration. Genome 2006a; 49: 195-204.
48. Heng HH, Stevens JB, Liu G, et al. Stochastic cancer progression driven by non-clonal chromosome aberrations. J Cell Physiol 2006b; 208: 461-72.
49. Heng HH, Bremer SW, Stevens J, et al. Cancer progression by non-clonal chromosome aberrations. J Cell Biochem 2006c; 98: 1424-35.
50. Bielas JH, Loeb KR, Rubin BP, et al. Human cancers express a mutator phenotype. Proc Natl Acad Sci USA 2006; 103: 18238-42.
51. Bayani J, Selvarajah S, Maire G, et al. Genomic mechanisms and measurement of structural and numerical instability in cancer cells. Semin Cancer Biol 2007; 17: 5-18.
52. Bartos JD, Gaile DP, McQuaid DE, et al. aCGH local copy number aberrations associated with overall copy number genomic instability in colorectal cancer: coordinate involvement of the regions including BCR and ABL. Mutat Res 2007; 615: 1-11.
53. Ye CJ, Liu G, Bremer SW, et al. The dynamics of cancer chromosomes and genomes. Cytogenet Genome Res 2007; 118: 237-46.
54. Heng HH, Bremer SW, Stevens JB, et al. Genetic and epigenetic heterogeneity in cancer: a genome-centric perspective. J Cell Physiol 2009; 220: 538-47.
55. Heng HH. The conflict between complex system and reductionism. JAMA 2008; 300: 1580-1.
56. Heng HH. The genome-centric concept: re-synthesis of evolutionary theory. BioEssays 2009; 31: 512-25.
57. Ye CJ, Lu W, Liu G, et al. The combination of SKY and specific loci detection with FISH or immunostaining. Cytogenet Cell Genet 2001; 93: 195-202.
58. Heng HH, Ye CJ, Yang F, et al. Analysis of marker or complex chromosomal rearrangements present in pre- and post-natal karyotypes utilizing a combination of G-banding, spectral karyotyping and fluorescence in situ hybridization. Clin Genet 2003; 63: 358-67.
59. Ye CJ, Stevens JB, Liu G, et al. Combined multicolor-FISH and immunostaining. Cytogenet Genome Res 2006; 114: 227-34.
60. Gould SJ, Eldredge N. Punctuated equilibrium comes of age. Nature 1993; 366: 223-7.
61. Heng HH, Stevens J, Bremer S, et al. The evolutionary mechanism of cancer. J Cell Biochem 2010; 109: 1072-84.
62. Atkin NB, Huang X. Are human cancers ever diploid - or often trisomic? an update. Cytogenet Cell Genet 2001; 92: 345-6.
63. Albertson DG, Collins C, McCormick F, et al. Chromosome aberrations in solid tumors. Nat Genet 2003; 34: 369-76.
64. Gossage L, Madhusudan S. Cancer pharmacogenomics: role of DNA repair genetic polymorphisms in individualizing cancer therapy. Mol Diagn Ther 2007; 11: 361-80.
65. Shlien A, Malkin D. Copy number variations and cancer susceptibility. Curr Opin Oncol 2010; 22: 55-63.
66. Skarda J, Amariglio N, Rechavi G. RNA editing in human cancer: review. APMIS 2009; 117: 551-7.
67. Passetti F, Ferreira CG, Costa FF. The impact of microRNAs and alternative splicing in pharmacogenomics. Pharmacogenom J 2009; 9: 1-13.
68. Wouters BG, Weppler SA, Koritzinsky M, et al. Hypoxia as a target for combined modality treatments. Eur J Cancer 2002; 38: 240-57.
69. Nelson CM, Bissell MJ. Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer. Annu Rev Cell Dev Biol 2006; 22: 287-309.
70. Rubin H. What keeps cells in tissues behaving normally in the face of myriad mutations? Bioessays 2006; 28: 515-24.
71. Gijsen R, Hoeymans N, Schellevis FG, et al. Causes and consequences of comorbidity: a review. J Clin Epidemiol 2001; 54: 661-74.
72. von Zglinicki T. Oxidative stress shortens telomeres. Trends Biochem Sci 2002; 27: 339-44.
73. Epel ES, Blackburn EH, Lin J, et al. Accelerated telomere shortening in response to life stress. Proc Natl Acad Sci USA 2004; 101: 17312-5.
74. Epel ES. Psychological and metabolic stress: a recipe for accelerated cellular aging? Hormones (Athens) 2009; 8: 7-22.
75. Milner JA. Nutrition and cancer: essential elements for a roadmap. Cancer Lett 2008; 269: 189-98.
76. Oakman C, Pestrin M, Cantisani E, Licitra S, DeStefanis M, Biganzoli L, Di Leo A. Adjuvant chemotherapy-the dark side of clinical trials. Have we learnt more? Breast. 2009; suppl 3: S18-24.
77. Heng HH. The gene-centric concept: a new liability? Bioessays 2008; 30: 196-7.
78. Ye CJ, Stevens JB, Liu G, et al. Genome based cell population heterogeneity promotes tumorigenicity: the evolutionary mechanism of cancer. J Cell Physiol 2009; 219: 288-300.
79. Durand PM, Michod RE. Genomics in the light of evolutionary transitions. Evolution 2009; 64: 1533-40.
80. Aebersold R, Auffray C, Baney E, et al. Report on EU-USA workshop: how systems biology can advance cancer research (27 October 2008). Mol Oncol 2009; 3: 9-17.
81. Heng HH, Chamberlain JW, Shi XM, et al. Regulation of meiotic chromatin loop size by chromosomal position. Proc Natl Acad Sci USA 1996; 93: 2795-800.
82. Heng HH, Spyropoulos B, Moens PB. FISH technology in chromosome and genome research. Bioessays 1997; 19: 75-84.
83. Heng HH, Krawetz SA, Lu W, et al. Re-defining the chromatin loop domain. Cytogenet Cell Genet 2001; 93: 155-61.
84. Heng HH, Goetze S, Ye CJ, et al. Chromatin loops are selectively anchored using scaffold/matrix-attachment regions. J Cell Sci 2004b; 117: 999-1008.
85. Nichol ST, Rowe JE, Fitch WM. Punctuated equilibrium and positive Darwinian evolution in vesicular stomatitis virus. Proc Natl Acad Sci USA 1993; 90: 10424-8.
86. Elena SF, Cooper VS, Lenski RE. Punctuated evolution caused by selection of rare beneficial mutations. Science 1996; 272: 1802-4.
87. Heng HH. Elimination of altered karyotypes by sexual reproduction preserves species identity. Genome 2007b; 50: 517-24.
88. Wilkins, AS, Holliday, R. The evolution of meiosis from mitosis. Genetics 2009; 181:3-12.
89. Glansdorff, N.; Xu, Y.; Labedan, D et al. The conflict between horizontal gene transfer and the safeguard of identity: origin of meiotic sexuality. J Mol Evol 2009; 69: 470-80.
90. Gorelick R, Carpinone J. Origin and maintenance of sex: the evolutionary joys of self sex: Biol J Linn Soc 2010; 98: 707-28.
91. Huang S. http://www.nature.com/nrc/journal/v2/n6/full/nrc819.html - a1 Opinion: Histone methyltransferases, diet nutrients and tumour suppressors. Nat Rev Cancer 2002; 2: 469-476.
92. Gaudet F, Hodgson JG, Eden A, et al. Induction of tumors in mice by genomic hypomethylation. Science 2003; 300: 489-92.
93. McCabe DC, Caudill MA. DNA methylation, genomic silencing, and links to nutrition and cancer. Nutr Rev 2005; 63: 183-95.
94. Nystrom M, Mutanen M. Diet and epigenetics in colon cancer. World J Gastroenterol 2009; 15: 257-263.
95. Xu GL, Bestor TH, Bourc'his D, et al. Chromosome instability and immunodeficiency syndrome caused by mutations in a DNA methyltransferase gene. Nature 1999; 402: 187-91.
96. Bestor TH. Transposons reanimated in mice. Cell 2005; 122: 322-5.
97. Greger V, Passarge E, Höpping W, et al. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet 1989; 83: 155-8.
98. Saito Y, Jones PA. Epigenetic activation of tumor suppressor microRNAs in human cancer cells. Cell Cycle 2006; 5: 2220-2.
99. Lederberg J, Lederberg EM. Replica plating and indirect selection of bacterial mutants. J Bacteriol 1952; 63: 399-406.
100. Brash D, Cairns J. The mysterious steps in carcinogenesis. Br J Cancer 2009; 101: 379-80.
101. Mittral I. The disconnection between tumor response and survival. Nat Clin Pract Oncol 2007; 4: 203.
102. Quintás-Cardama A, Kantarjian H, Cortes J. Imatinib and beyond-exploring the full potential of targeted therapy for CML. Nat Rev Clin Oncol 2009; 6: 535-43.
103. Rancati G, Pavelka N, Fleharty B, et al. Aneuploidy underlies rapid adaptive evolution of yeast cells deprived of a conserved cytokinesis motor. Cell 2008; 135: 879-93.
104. Tew KD; Moy BC; Hartley-Asp B. Acquired drug resistance is accompanied by modification in the karyotype and nuclear matrix of a rat carcinoma cell line. Exper Cell Res 1983; 149: 443-50.
105. Weise A, Liehr T, Efferth T, et al. Comparative M-FISH and CGH analyses in sensitive and drug-resistant human T-cell acute leukemia cell lines. Cytogenet Genome Res 2002; 98: 118-25.
106. McClelland SE, Burrell RA, Swanton C. Chromosomal instability: a composite phenotype that influences sensitivity to chemotherapy. Cell Cycle 2009; 8: 3262-6.
107. Duesberg P, Li R, Sachs R, et al. Cancer drug resistance: the central role of the karyotype. Drug Resist Update 2007;10:51-8.
108. Walther A, Houlston R, Tomlinson I. Association between chromosomal instability and prognosis in colorectal cancer: a meta-analysis. Gut. 2008;57:941-50.
109. Lemoli RM, Salvestrini V, Bianchi E, et al. Molecular and functional analysis of the stem cell compartment of chronic myelogenous leukemia reveals the presence of a CD34- cell population with intrinsic resistance to imatinib. Blood 2009;114:5191-200.
110. Cahill DP, Kinzler KW, Vogelstein B, et al. Genetic instability and darwinian selection in tumours. Trends Cell Biol 1999; 9: M57-60.
111. Weaver BA, Silk AD, Montagna C, et al. Aneuploidy acts both oncogenically and as a tumor suppressor. Cancer Cell. 2007; 11: 25-36.
112. Breivik J. The evolutionary origin of genetic instability in cancer development. Semin Cancer Biol 2005; 15: 51-60.
113. Lengauer C, Kinzler KW, Vogelstein B. Genetic instabilities in human cancers. Nature 1998; 396: 643-9.
114. de la Chapelle A. Microsatellite instability. N Engl J Med 2003; 349: 209-210.
115. Atkin NB. Microsatellite instability. Cytogenet Cell Genet 2001; 92: 177-181.
116. Dunn KL, He S, Wark L, et al. Increased genomic instability and altered chromosomal protein phosphorylation timing in HRAS- transformed mouse fibroblasts. Genes Chromosomes Cancer 2009; 48: 397-409.
117. Loeb, K.R. and Loeb, L.A. (1999). Genetic instability and the mutator phenotype studies in ulcerative colitis. Am J Pathol 1999; 154: 1621-1626.
118. Park SY, Gönen M, Kim HJ, Cellular and genetic diversity in the progression of in situ human breast carcinomas to an invasive phenotype. J Clin Invest 2010; 120: 636-644.
119. Duesberg P, Stindl R, Hehlmann R. Explaining the high mutation rates of cancer cells to drug and multidrug resistance by chromosome reassortments that are catalyzed by aneuploidy. Proc Natl Acad Sci USA 2000; 97: 14295-300.
120. Duesberg P, Li R, Fabarius A, et al. Aneuploidy and cancer: from correlation to causation. Contrib Microbiol 2006; 13: 16-44.
121. Shen KC, Heng H, Wang Y, et al. ATM and p21cooperate to suppress aneuploidy and subsequent tumor development. Cancer Res 2005; 65: 8747-53.
122. Gao C, Furge K, Koeman J, et al. Chromosome instability, chromosome transcriptome, and clonal evolution of tumor cell populations. Proc Natl Acad Sci USA 2007; 104: 8995-9000.
123. Roschke AV, Lababidi S, Tonon G, et al. Karyotypic state as a potential determinant for anticancer drug discovery. Proc Natl Acad Sci USA 2005; 102: 2964-9.
124. Graham JS, Kaye SB, Brown R. The promises and pitfalls of epigenetic therapies in solid tumours. Eur J Cancer 2009; 45:1129-36.
125. Mulero-Navarro S, Esteller M. Chromatin remodeling factor CHD5 is silenced by promoter CpG island hypermethylation in human cancer. Epigenetics 2008; 3: 210-5.
126. Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet 2006; 7: 21-33.
127. Postovit LM, Costa FF, Bischof JM, et al. The commonality of plasticity underlying multipotent tumor cells and embryonic stem cells. J Cell Biochem 2007; 101: 908-17.
128. Fraga MF, Herranz M, Espada J, et al. A mouse skin multistage carcinogenesis model reflects the aberrant DNA methylation patterns of human tumors. Cancer Res 2004; 64: 5527-34.
129. Lyko F, Brown R. DNA methyltransferase inhibitors and the development of epigenetic cancer therapies. J Natl Cancer Inst 2005; 97:1498-506.
130. Esteller M. Epigenetics in cancer. N Engl J Med 2008; 358: 1148-59.
131. Whittington PJ, Piechocki MP, Heng HH, et al. DNA vaccination controls Her-2+ tumors that are refractory to targeted therapies. Cancer Res 2008; 68: 7502-11.
132. Ellis LM, Hicklin DJ. Pathways mediating resistance to vascular endothelial growth factor-targeted therapy. Clin Cancer Res 2008; 14: 6371-6375.
133. Reynolds AR, Hart IR, Watson AR, et al. Stimulation of tumor growth and angiogenesis by low concentrations of RGD-mimetic integrin inhibitors. Nat Med. 2009; 15:392-400.
134. Don AS, Hogg PJ. Mitochondria as cancer drug targets. Trends Mol Med 2004; 10: 372-8.
135. Ralph SJ, Neuzil J. Mitochondria as targets for cancer therapy. Mol Nutr Food Res. 2009; 53: 9-28.
136. Bonnet S, Archer SL, Allalunis-Turner J, et al. A mitochondria-K+ channel axis is suppressed in cancer and its normalization promotes apoptosis and inhibits cancer growth. Cancer Cell 2007; 11: 37-51.
137. Hornberg JJ, Bruggeman FJ, Westerhoff HV, et al. Cancer: a Systems Biology disease. Biosystems 2006; 83: 81-90.
138. Xie L, Li J, Xie L, et al. Drug Discovery Using Chemical Systems Biology: Identification of the Protein-Ligand Binding Network To Explain the Side Effects of CETP Inhibitors. PLoS Comput Biol 2009; 5: e1000387.
139. Araujo RP, Liotta LA, Petricoin EF. Proteins, drug targets and the mechanisms they control: the simple truth about complex networks. Nat Rev Drug Discov 2007; 6: 871-80.
140. Ganter B, Giroux CN. Emerging applications of network and pathway analysis in drug discovery and development. Curr Opin Drug Discov Devel 2008; 11: 86-94.