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  • Historical Perspective
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Cancer genes and the pathways they control

Nature Medicine volume 10, pages 789–799 (2004)Cite this article

Abstract

The revolution in cancer research can be summed up in a single sentence: cancer is, in essence, a genetic disease. In the last decade, many important genes responsible for the genesis of various cancers have been discovered, their mutations precisely identified, and the pathways through which they act characterized. The purposes of this review are to highlight examples of progress in these areas, indicate where knowledge is scarce and point out fertile grounds for future investigation.

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Figure 1: Receptor tyrosine kinase (RTK) pathway.
Figure 2: Rb (a) and p53 (b) pathways.
Figure 3: Apoptosis pathway.
Figure 4: HIF1 pathway.
Figure 5: APC pathway.
Figure 6: GLI pathway.
Figure 7: PI3K pathway.
Figure 8: SMAD pathway.
Figure 9: Overview of cancer gene pathways.

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References

  1. Davies, H. et al. Mutations of the BRAF gene in human cancer. Nature 417, 949–954 (2002).

    Article  CAS  PubMed  Google Scholar 

  2. Wan, P.T. et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell 116, 855–867 (2004).

    Article  CAS  PubMed  Google Scholar 

  3. Santarosa, M. & Ashworth, A. Haploinsufficiency for tumour suppressor genes: when you don't need to go all the way. Biochim. Biophys. Acta 1654, 105–122 (2004).

    CAS  PubMed  Google Scholar 

  4. Knudson, A.G. Cancer genetics. Am. J. Med. Genet. 111, 96–102 (2002).

    Article  PubMed  Google Scholar 

  5. Friedberg, E.C. DNA damage and repair. Nature 421, 436–440 (2003).

    Article  PubMed  CAS  Google Scholar 

  6. Nowell, P.C. Tumor progression: a brief historical perspective. Semin. Cancer Biol. 12, 261–266 (2002).

    Article  CAS  PubMed  Google Scholar 

  7. 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).

    Article  CAS  PubMed  Google Scholar 

  8. Van Dyke, T. & Jacks, T. Cancer modeling in the modern era: progress and challenges. Cell 108, 135–144 (2002).

    Article  CAS  PubMed  Google Scholar 

  9. Horvitz, H.R. Worms, life, and death. Chembiochem 4, 697–711 (2003).

    Article  CAS  PubMed  Google Scholar 

  10. Sherr, C.J. Cancer cell cycles revisited. Cancer Res. 60, 3689–3695 (2000).

    CAS  PubMed  Google Scholar 

  11. Ortega, S., Malumbres, M. & Barbacid, M. Cyclin D-dependent kinases, INK4 inhibitors and cancer. Biochim. Biophys. Acta 1602, 73–87 (2002).

    CAS  PubMed  Google Scholar 

  12. Classon, M. & Harlow, E. The retinoblastoma tumour suppressor in development and cancer. Nat. Rev. Cancer 2, 910–917 (2002).

    Article  CAS  PubMed  Google Scholar 

  13. Ichimura, K. et al. Deregulation of the p14ARF/MDM2/p53 pathway is a prerequisite for human astrocytic gliomas with G1-S transition control gene abnormalities. Cancer Res. 60, 417–424 (2000).

    CAS  PubMed  Google Scholar 

  14. Vogelstein, B., Lane, D. & Levine, A.J. Surfing the p53 network. Nature 408, 307–310 (2000).

    Article  CAS  PubMed  Google Scholar 

  15. Oren, M. Decision making by p53: life, death and cancer. Cell Death Differ. 10, 431–442 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Prives, C. & Hall, P.A. The p53 pathway. J. Pathol. 187, 112–126 (1999).

    Article  CAS  PubMed  Google Scholar 

  17. Klein, G. Perspectives in studies of human tumor viruses. Front. Biosci. 7, d268–d274 (2002).

    Article  CAS  PubMed  Google Scholar 

  18. Munger, K. & Howley, P.M. Human papillomavirus immortalization and transformation functions. Virus Res. 89, 213–228 (2002).

    Article  CAS  PubMed  Google Scholar 

  19. zur Hausen, H. Oncogenic DNA viruses. Oncogene 20, 7820–7823 (2001).

    Article  CAS  PubMed  Google Scholar 

  20. Hunter, T. Signaling–2000 and beyond. Cell 100, 113–127 (2000).

    Article  CAS  PubMed  Google Scholar 

  21. Komarova, N.L., Sengupta, A. & Nowak, M.A. Mutation-selection networks of cancer initiation: tumor suppressor genes and chromosomal instability. J. Theor. Biol. 223, 433–450 (2003).

    Article  CAS  PubMed  Google Scholar 

  22. Rowley, J.D. The critical role of chromosome translocations in human leukemias. Annu. Rev. Genet. 32, 495–519 (1998).

    Article  CAS  PubMed  Google Scholar 

  23. Mitelman, F. Recurrent chromosome aberrations in cancer. Mutat. Res. 462, 247–253 (2000).

    Article  CAS  PubMed  Google Scholar 

  24. Verheul, H.M., Voest, E.E. & Schlingemann, R.O. Are tumours angiogenesis-dependent? J. Pathol. 202, 5–13 (2004).

    Article  CAS  PubMed  Google Scholar 

  25. Tlsty, T.D. & Hein, P.W. Know thy neighbor: stromal cells can contribute oncogenic signals. Curr. Opin. Genet. Dev. 11, 54–59 (2001).

    Article  CAS  PubMed  Google Scholar 

  26. Fata, J.E., Werb, Z. & Bissell, M.J. Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes. Breast Cancer Res. 6, 1–11 (2004).

    Article  CAS  PubMed  Google Scholar 

  27. Kerbel, R. & Folkman, J. Clinical translation of angiogenesis inhibitors. Nat. Rev. Cancer 2, 727–739 (2002).

    Article  CAS  PubMed  Google Scholar 

  28. Folkman, J. Role of angiogenesis in tumor growth and metastasis. Semin. Oncol. 29, 15–18 (2002).

    Article  CAS  PubMed  Google Scholar 

  29. Ferrara, N., Hillan, K.J., Gerber, H.P. & Novotny, W. Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discov. 3, 391–400 (2004).

    Article  CAS  PubMed  Google Scholar 

  30. Kondo, K., Klco, J., Nakamura, E., Lechpammer, M. & Kaelin, W.G. Jr. Inhibition of HIF is necessary for tumor suppression by the von Hippel-Lindau protein. Cancer Cell 1, 237–246 (2002).

    Article  CAS  PubMed  Google Scholar 

  31. Semenza, G.L. Targeting HIF-1 for cancer therapy. Nat. Rev. Cancer 3, 721–732 (2003).

    Article  CAS  PubMed  Google Scholar 

  32. Strausberg, R.L., Simpson, A.J. & Wooster, R. Sequence-based cancer genomics: progress, lessons and opportunities. Nat. Rev. Genet. 4, 409–418 (2003).

    Article  CAS  PubMed  Google Scholar 

  33. Loeb, L.A., Loeb, K.R. & Anderson, J.P. Multiple mutations and cancer. Proc. Natl. Acad. Sci. USA 100, 776–781 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rajagopalan, H., Nowak, M.A., Vogelstein, B. & Lengauer, C. The significance of unstable chromosomes in colorectal cancer. Nat. Rev. Cancer 3, 695–701 (2003).

    Article  CAS  PubMed  Google Scholar 

  35. Sieber, O.M., Heinimann, K. & Tomlinson, I.P. Genomic instability—the engine of tumorigenesis? Nat. Rev. Cancer 3, 701–708 (2003).

    Article  CAS  PubMed  Google Scholar 

  36. Wang, T.L. et al. Prevalence of somatic alterations in the colorectal cancer cell genome. Proc. Natl. Acad. Sci. USA 99, 3076–3080 (2002).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Lengauer, C., Kinzler, K.W. & Vogelstein, B. Genetic instabilities in human cancers. Nature 396, 643–649 (1998).

    Article  CAS  PubMed  Google Scholar 

  38. Duesberg, P. & Li, R. Multistep carcinogenesis: a chain reaction of aneuploidizations. Cell Cycle 2, 202–210 (2003).

    Article  CAS  PubMed  Google Scholar 

  39. Albertson, D.G. & Pinkel, D. Genomic microarrays in human genetic disease and cancer. Hum. Mol. Genet. 12 (spec. no. 2), R145–R152 (2003).

    Article  CAS  PubMed  Google Scholar 

  40. Shiloh, Y. & Kastan, M.B. ATM: genome stability, neuronal development, and cancer cross paths. Adv. Cancer Res. 83, 209–254 (2001).

    Article  CAS  PubMed  Google Scholar 

  41. Scully, R. & Livingston, D.M. In search of the tumour-suppressor functions of BRCA1 and BRCA2. Nature 408, 429–432 (2000).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Maser, R.S. & DePinho, R.A. Connecting chromosomes, crisis, and cancer. Science 297, 565–569 (2002).

    Article  CAS  PubMed  Google Scholar 

  43. Pihan, G. & Doxsey, S.J. Mutations and aneuploidy: co-conspirators in cancer? Cancer Cell 4, 89–94 (2003).

    Article  CAS  PubMed  Google Scholar 

  44. Rajagopalan, H. et al. Inactivation of hCDC4 can cause chromosomal instability. Nature 428, 77–81 (2004).

    Article  CAS  PubMed  Google Scholar 

  45. Shay, J.W. & Roninson, I.B. Hallmarks of senescence in carcinogenesis and cancer therapy. Oncogene 23, 2919–2933 (2004).

    Article  CAS  PubMed  Google Scholar 

  46. Chambers, A.F., Groom, A.C. & MacDonald, I.C. Dissemination and growth of cancer cells in metastatic sites. Nat. Rev. Cancer 2, 563–572 (2002).

    Article  CAS  PubMed  Google Scholar 

  47. Fidler, I.J. Critical determinants of metastasis. Semin. Cancer Biol. 12, 89–96 (2002).

    Article  PubMed  Google Scholar 

  48. Hunter, K.W. Host genetics and tumour metastasis. Br. J. Cancer 90, 752–755 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Hruban, R.H., Goggins, M., Parsons, J. & Kern, S.E. Progression model for pancreatic cancer. Clin. Cancer Res. 6, 2969–2972 (2000).

    CAS  PubMed  Google Scholar 

  50. Aguirre, A.J. et al. Activated Kras and Ink4a/Arf deficiency cooperate to produce metastatic pancreatic ductal adenocarcinoma. Genes Dev. 17, 3112–3126 (2003).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  51. Jen, J. et al. Molecular determinants of dysplasia in colorectal lesions. Cancer Res. 54, 5523–5526 (1994).

    CAS  PubMed  Google Scholar 

  52. Pretlow, T.P. Aberrant crypt foci and K-ras mutations: earliest recognized players or innocent bystanders in colon carcinogenesis? Gastroenterology 108, 600–603 (1995).

    Article  CAS  PubMed  Google Scholar 

  53. Sieben, N.L. et al. In ovarian neoplasms, BRAF, but not KRAS, mutations are restricted to low-grade serous tumours. J. Pathol. 202, 336–340 (2004).

    Article  CAS  PubMed  Google Scholar 

  54. Kinzler, K.W. & Vogelstein, B. Colorectal Tumors. in The Genetic Basis of Human Cancer (eds. Vogelstein, B. & Kinzler, K.W.) 565–587 (McGraw-Hill, New York, 1998).

    Google Scholar 

  55. Barbacid, M. ras genes. Annu. Rev. Biochem. 56, 779–827 (1987).

    Article  CAS  PubMed  Google Scholar 

  56. Bos, J.L. ras oncogenes in human cancer: a review. Cancer Res. 49, 4682–4689 (1989).

    CAS  PubMed  Google Scholar 

  57. Zhang, Z. et al. Wildtype Kras2 can inhibit lung carcinogenesis in mice. Nat. Genet. 29, 25–33 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Diaz, R. et al. The N-ras proto-oncogene can suppress the malignant phenotype in the presence or absence of its oncogene. Cancer Res. 62, 4514–4518 (2002).

    CAS  PubMed  Google Scholar 

  59. Bronner-Fraser, M. Development. Making sense of the sensory lineage. Science 303, 966–968 (2004).

    Article  CAS  PubMed  Google Scholar 

  60. Jiricny, J. Eukaryotic mismatch repair: an update. Mutat. Res. 409, 107–121 (1998).

    Article  CAS  PubMed  Google Scholar 

  61. Fishel, R. & Wilson, T. MutS homologs in mammalian cells. Curr. Opin. Genet. Dev. 7, 105–113 (1997).

    Article  CAS  PubMed  Google Scholar 

  62. Lynch, H.T. & de la Chapelle, A. Hereditary colorectal cancer. N. Engl. J. Med. 348, 919–932 (2003).

    Article  CAS  PubMed  Google Scholar 

  63. Yamamoto, H., Imai, K. & Perucho, M. Gastrointestinal cancer of the microsatellite mutator phenotype pathway. J. Gastroenterol. 37, 153–163 (2002).

    Article  CAS  PubMed  Google Scholar 

  64. Honchel, R., Halling, K.C. & Thibodeau, S.N. Genomic instability in neoplasia. Semin. Cell Biol. 6, 45–52 (1995).

    Article  CAS  PubMed  Google Scholar 

  65. Brown, P.O. & Botstein, D. Exploring the new world of the genome with DNA microarrays. Nat. Genet. 21, 33–37 (1999).

    Article  CAS  PubMed  Google Scholar 

  66. Polyak, K. & Riggins, G.J. Gene discovery using the serial analysis of gene expression technique: implications for cancer research. J. Clin. Oncol. 19, 2948–2958 (2001).

    Article  CAS  PubMed  Google Scholar 

  67. Jones, P.A. & Baylin, S.B. The fundamental role of epigenetic events in cancer. Nat. Rev. Genet. 3, 415–428 (2002).

    Article  CAS  PubMed  Google Scholar 

  68. Feinberg, A.P. & Tycko, B. The history of cancer epigenetics. Nat. Rev. Cancer 4, 143–153 (2004).

    Article  CAS  PubMed  Google Scholar 

  69. Collins, F.S., Green, E.D., Guttmacher, A.E. & Guyer, M.S. A vision for the future of genomics research. Nature 422, 835–847 (2003).

    Article  CAS  PubMed  Google Scholar 

  70. Schadt, E.E., Monks, S.A. & Friend, S.H. A new paradigm for drug discovery: integrating clinical, genetic, genomic and molecular phenotype data to identify drug targets. Biochem. Soc. Trans. 31, 437–443 (2003).

    Article  CAS  PubMed  Google Scholar 

  71. Paddison, P.J. et al. A resource for large-scale RNA-interference-based screens in mammals. Nature 428, 427–431 (2004).

    Article  CAS  PubMed  Google Scholar 

  72. Berns, K. et al. A large-scale RNAi screen in human cells identifies new components of the p53 pathway. Nature 428, 431–437 (2004).

    Article  CAS  PubMed  Google Scholar 

  73. Rosenblatt, K.P. et al. Serum proteomics in cancer diagnosis and management. Annu. Rev. Med. 55, 97–112 (2004).

    Article  CAS  PubMed  Google Scholar 

  74. Luo, J., Isaacs, W.B., Trent, J.M. & Duggan, D.J. Looking beyond morphology: cancer gene expression profiling using DNA microarrays. Cancer Invest. 21, 937–949 (2003).

    Article  CAS  PubMed  Google Scholar 

  75. Ma, X.J. et al. A two-gene expression ratio predicts clinical outcome in breast cancer patients treated with tamoxifen. Cancer Cell 5, 607–616 (2004).

    Article  CAS  PubMed  Google Scholar 

  76. Futreal, P.A. et al. A census of human cancer genes. Nat. Rev. Cancer 4, 177–183 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  77. Masayesva, B.G. et al. Gene expression alterations over large chromosomal regions in cancers include multiple genes unrelated to malignant progression. Proc. Natl. Acad. Sci. USA 101, 8715–8720 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Stewart, S.A. & Weinberg, R.A. Senescence: does it all happen at the ends? Oncogene 21, 627–630 (2002).

    Article  CAS  PubMed  Google Scholar 

  79. Feldser, D.M., Hackett, J.A. & Greider, C.W. Telomere dysfunction and the initiation of genome instability. Nat. Rev. Cancer 3, 623–627 (2003).

    Article  CAS  PubMed  Google Scholar 

  80. Chan, S.R. & Blackburn, E.H. Telomeres and telomerase. Phil. Trans. R. Soc. Lond. B 359, 109–121 (2004).

    Article  CAS  Google Scholar 

  81. Cech, T.R. Beginning to understand the end of the chromosome. Cell 116, 273–279 (2004).

    Article  CAS  PubMed  Google Scholar 

  82. Miklos, G.L. & Maleszka, R. Microarray reality checks in the context of a complex disease. Nat. Biotechnol. 22, 615–621 (2004).

    Article  CAS  PubMed  Google Scholar 

  83. Hope, K.J., Jin, L. & Dick, J.E. Human acute myeloid leukemia stem cells. Arch. Med. Res. 34, 507–514 (2003).

    Article  CAS  PubMed  Google Scholar 

  84. Berking, C. & Herlyn, M. Human skin reconstruct models: a new application for studies of melanocyte and melanoma biology. Histol. Histopathol. 16, 669–674 (2001).

    CAS  PubMed  Google Scholar 

  85. Kuperwasser, C. et al. Reconstruction of functionally normal and malignant human breast tissues in mice. Proc. Natl Acad. Sci. USA 101, 4966–4971 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Frei, E.I. & Eder, J.P. Principles of dose, schedule, and combination Therapy. in Cancer Medicine (eds. Kufe, D.W. et al.) 669–677 (B.C. Decker, Inc., Hamilton, Ontario, 2003).

    Google Scholar 

  87. Pegram, M.D., Konecny, G. & Slamon, D.J. The molecular and cellular biology of HER2/neu gene amplification/overexpression and the clinical development of herceptin (trastuzumab) therapy for breast cancer. Cancer Treat. Res. 103, 57–75 (2000).

    Article  CAS  PubMed  Google Scholar 

  88. Druker, B.J. et al. Chronic myelogenous leukemia. in Hematology 2001 (American Society of Hematology Education Program) 87–112 (American Society of Hematology, 2001).

    Google Scholar 

  89. Mechtersheimer, G. et al. Gastrointestinal stromal tumours and their response to treatment with the tyrosine kinase inhibitor imatinib. Virchows Arch. 444, 108–118 (2004).

    Article  CAS  PubMed  Google Scholar 

  90. Langer, C.J. Emerging role of epidermal growth factor receptor inhibition in therapy for advanced malignancy: focus on NSCLC. Int. J. Radiat. Oncol. Biol. Phys. 58, 991–1002 (2004).

    Article  CAS  PubMed  Google Scholar 

  91. Duensing, A., Heinrich, M.C., Fletcher, C.D. & Fletcher, J.A. Biology of gastrointestinal stromal tumors: KIT mutations and beyond. Cancer Invest. 22, 106–116 (2004).

    Article  CAS  PubMed  Google Scholar 

  92. Paez, J.G. et al. EGFR mutations in lung cancer: correlation with clinical response to gefitinib therapy. Science 304, 1497–1500 (2004).

    Article  CAS  PubMed  Google Scholar 

  93. Lynch, T.J. et al. Activating mutations in the epidermal growth factor receptor underlying responsiveness of non-small-cell lung cancer to gefitinib. N. Engl. J. Med. 350, 2129–2139 (2004).

    Article  CAS  PubMed  Google Scholar 

  94. Schmitt, C.A. & Lowe, S.W. Apoptosis and therapy. J. Pathol. 187, 127–137 (1999).

    Article  CAS  PubMed  Google Scholar 

  95. Danial, N.N. & Korsmeyer, S.J. Cell death: critical control points. Cell 116, 205–219 (2004).

    Article  CAS  PubMed  Google Scholar 

  96. Brown, J.M. & Wouters, B.G. Apoptosis: mediator or mode of cell killing by anticancer agents? Drug Resist. Updat. 4, 135–136 (2001).

    Article  CAS  PubMed  Google Scholar 

  97. Weinstein, I.B. et al. Disorders in cell circuitry associated with multistage carcinogenesis: exploitable targets for cancer prevention and therapy. Clin. Cancer Res. 3, 2696–2702 (1997).

    CAS  PubMed  Google Scholar 

  98. Nygren, P. & Larsson, R. Overview of the clinical efficacy of investigational anticancer drugs. J. Intern. Med. 253, 46–75 (2003).

    Article  CAS  PubMed  Google Scholar 

  99. Shih, L.Y. et al. Heterogeneous patterns of FLT3 Asp(835) mutations in relapsed de novo acute myeloid leukemia: a comparative analysis of 120 paired diagnostic and relapse bone marrow samples. Clin. Cancer Res. 10, 1326–1332 (2004).

    Article  CAS  PubMed  Google Scholar 

  100. Kinzler, K.W. & Vogelstein, B. Lessons from hereditary colon cancer. Cell 87, 159–170 (1996).

    Article  CAS  PubMed  Google Scholar 

  101. Weissleder, R. & Ntziachristos, V. Shedding light onto live molecular targets. Nat. Med. 9, 123–128 (2003).

    Article  CAS  PubMed  Google Scholar 

  102. Sidransky, D. Emerging molecular markers of cancer. Nat. Rev. Cancer 2, 210–219 (2002).

    Article  CAS  PubMed  Google Scholar 

  103. Gschwind, A., Fischer, O.M. & Ullrich, A. The discovery of receptor tyrosine kinases: targets for cancer therapy. Nat. Rev. Cancer 4, 361–370 (2004).

    Article  CAS  PubMed  Google Scholar 

  104. Downward, J. Targeting RAS signalling pathways in cancer therapy. Nat. Rev. Cancer 3, 11–22 (2003).

    Article  CAS  PubMed  Google Scholar 

  105. Malumbres, M. & Barbacid, M. To cycle or not to cycle: a critical decision in cancer. Nat. Rev. Cancer 1, 222–231 (2001).

    Article  CAS  PubMed  Google Scholar 

  106. Giles, R.H., van Es, J.H. & Clevers, H. Caught up in a Wnt storm: Wnt signaling in cancer. Biochim. Biophys. Acta 1653, 1–24 (2003).

    CAS  PubMed  Google Scholar 

  107. Cantley, L.C. The phosphoinositide 3-kinase pathway. Science 296, 1655–1657 (2002).

    Article  CAS  PubMed  Google Scholar 

  108. Shi, Y. & Massague, J. Mechanisms of TGF-β signaling from cell membrane to the nucleus. Cell 113, 685–700 (2003).

    Article  CAS  PubMed  Google Scholar 

  109. Ruiz i Altaba. A., Stecca, B. & Sanchez, P. Hedgehog–Gli signaling in brain tumors: stem cells and paradevelopmental programs in cancer. Cancer Lett. 204, 145–157 (2004).

    Article  CAS  PubMed  Google Scholar 

  110. Adams, J.M. Ways of dying: multiple pathways to apoptosis. Genes Dev. 17, 2481–2495 (2003).

    Article  CAS  PubMed  Google Scholar 

  111. Blagosklonny, M.V. & Pardee, A.B. The restriction point of the cell cycle. Cell Cycle 1, 103–110 (2002).

    CAS  PubMed  Google Scholar 

  112. Plas, D.R. & Thompson, C.B. Cell metabolism in the regulation of programmed cell death. Trends Endocrinol. Metab. 13, 75–78 (2002).

    Article  PubMed  Google Scholar 

  113. Green, D.R. & Evan, G.I. A matter of life and death. Cancer Cell 1, 19–30 (2002).

    Article  CAS  PubMed  Google Scholar 

  114. Eng, C., Kiuru, M., Fernandez, M.J. & Aaltonen, L.A. A role for mitochondrial enzymes in inherited neoplasia and beyond. Nat. Rev. Cancer 3, 193–202 (2003).

    Article  CAS  PubMed  Google Scholar 

  115. Lum, L. & Beachy, P.A. The Hedgehog response network: sensors, switches, and routers. Science 304, 1755–1759 (2004).

    Article  CAS  PubMed  Google Scholar 

  116. Brivanlou, A.H. & Darnell, J.E. Jr. Signal transduction and the control of gene expression. Science 295, 813–818 (2002).

    Article  CAS  PubMed  Google Scholar 

  117. Vogelstein, B. & Kinzler, K.W. The Genetic Basis of Human Cancer (McGraw-Hill, Toronto, 2002).

    Google Scholar 

  118. Cameron, E.R. & Neil, J.C. The Runx genes: lineage-specific oncogenes and tumor suppressors. Oncogene 23, 4308–4314 (2004).

    Article  CAS  PubMed  Google Scholar 

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Acknowledgements

The authors thank many colleagues for their critical reading of the manuscript and S. Mousses for sharing results on EphB2 before publication. Work in the authors' laboratories has been supported by the Ludwig Trust, the National Colorectal Cancer Research Alliance, the Miracle Foundation, the Clayton Fund and US National Institutes of Health grants CA43460, CA57345 and CA62924.

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  1. Howard Hughes Medical Institute and The Sidney Kimmel Comprehensive Cancer Center, The Johns Hopkins University Medical Institutions, Baltimore, 21231, Maryland, USA

    Bert Vogelstein & Kenneth W Kinzler

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Under separate licensing agreements between the Johns Hopkins University and Genzyme, Exact Sciences Corporation, Wyeth, Agencourt Biosciences, Hoffman-LaRoche, Merck and GMP Companies, the authors are entitled to a share of royalty received by the University on sales of products related to research described in this review. The authors and the University own Genzyme and GMP Companies stock, which is subject to certain restrictions under University policy. K.W.K. is a consultant to Genzyme and B.V. and K.W.K. are consultants to GMP Companies. K.W.K. receives research funding from Genzyme. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies.

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Vogelstein, B., Kinzler, K. Cancer genes and the pathways they control. Nat Med 10, 789–799 (2004). https://doi.org/10.1038/nm1087

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