The field of cancer biology has recently come of age, as witnessed by the initiation of this Annual Reviews journal this year. In this article, I argue that the major sources of cancer biology reside neither in cell biology nor in traditional cancer research, but instead in the domain once called “tumor virology.” Speaking from the perspective of someone who “rode the wave” that uncovered cancer genes and their effects on cell behavior, I have tried to trace the influences, discoveries, and changing attitudes and practices that produced the vibrant scientific landscape that we now enjoy.


Article metrics loading...

Loading full text...

Full text loading...


Literature Cited

  1. Alberts B, Kirschner MW, Tilghman S, Varmus H. 2014. Rescuing US biomedical research from its systemic flaws. PNAS 111:5773–77 [Google Scholar]
  2. Baltimore D. 1970. RNA-dependent DNA polymerase in virions of RNA tumour viruses. Nature 226:1209–11 [Google Scholar]
  3. Berget SM, Moore C, Sharp PA. 1977. Spliced segments at the 5′ terminus of adenovirus 2 late mRNA. PNAS 74:3171–75 [Google Scholar]
  4. Bernstein A, MacCormick R, Martin GS. 1976. Transformation-defective mutants of avian sarcoma viruses: the genetic relationship between conditional and nonconditional mutants. Virology 70:206–9 [Google Scholar]
  5. Bishop JM. 2003. How to Win the Nobel Prize: An Unexpected Life in Science Cambridge, MA: Harvard Univ. Press [Google Scholar]
  6. Bishop M, Varmus H. 1982. Functions and origins of retroviral transforming genes. See Weiss et al. 1982 999–1108
  7. Blackburn EH. 2010. Telomeres and telomerase: the means to the end (Nobel lecture). Angew. Chem. Int. Ed. Engl. 49:7405–21 [Google Scholar]
  8. Blumberg BS, London WT. 1982. Hepatitis B virus: pathogenesis and prevention of primary cancer of the liver. Cancer 50:2657–65 [Google Scholar]
  9. Bourne HR, Sanders DA, McCormick F. 1990. The GTPase superfamily: a conserved switch for diverse cell functions. Nature 348:125–32 [Google Scholar]
  10. Boveri T. 1915. Concerning the origin of malignant tumours by Theodor Boveri,. transl. annot. H Harris, 2008, in J. Cell Sci. 121:1–84 [Google Scholar]
  11. Brown PO. 1997. Integration. See Coffin et al. 1997 161–203
  12. Brush GS, Kelly TJ, Stillman B. 1995. Identification of eukaryotic DNA replication proteins using simian virus 40 in vitro replication system. Methods Enzymol 262:522–48 [Google Scholar]
  13. Cancer Genome Atlas Res. Netw. 2014. Comprehensive molecular characterization of gastric adenocarcinoma. Nature 513:202–9 [Google Scholar]
  14. Chang Y, Cesarman E, Pessin MS, Lee F, Culpepper J. et al. 1994. Identification of herpes virus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science 266:1865–69 [Google Scholar]
  15. Coffin JM, Hughes SH, Varmus H. 1997. Retroviruses Woodbury, NY: Cold Spring Harb. Lab. Press [Google Scholar]
  16. Coffin JM, Varmus HE, Bishop JM, Essex M, Hardy WD Jr. et al. 1981. Proposal for naming host cell-derived inserts in retrovirus genomes. J. Virol. 40:953–57 [Google Scholar]
  17. Crawford LV, Lane DP, Denhardt DT, Harlow EE, Nicklin PM. et al. 1980. Characterization of the complex between SV40 large T antigen and the 53K host protein in transformed mouse cells. Cold Spring Harb. Symp. Quant. Biol. 44:Pt. 1179–87 [Google Scholar]
  18. Der CJ, Krontiris TG, Cooper GM. 1982. Transforming genes of human bladder and lung carcinoma cell lines are homologous to the ras genes of Harvey and Kirsten sarcoma viruses. PNAS 79:3637–40 [Google Scholar]
  19. DeVita VT Jr., DeVita-Raeburn E. 2015. The Death of Cancer: After Fifty Years on the Front Lines of Medicine, A Pioneering Oncologist Reveals Why the War on Cancer Is Winnable—And How We Can Get There New York, NY: Sarah Crichton [Google Scholar]
  20. Druker BJ, Talpaz M, Resta DJ, Peng B, Buchdunger E. et al. 2001. Efficacy and safety of a specific inhibitor of the BCR-ABL tyrosine kinase in chronic myeloid leukemia. N. Engl. J. Med. 344:1031–37 [Google Scholar]
  21. Duesberg PH, Vogt PK. 1970. Differences between the ribonucleic acids of transforming and nontransforming avian tumor viruses. PNAS 67:1673–80 [Google Scholar]
  22. Fei DL, Motowski H, Chatrikhi R, Prasad S, Yu J. et al. 2016. Wild-type U2AF1 antagonizes the splicing program characteristic of U2AF1-mutant tumors and is required for cell survival. PLOS Genet. 12e1006384 [Google Scholar]
  23. Feng H, Shuda M, Chang Y, Moore PS. 2008. Clonal integration of a polyomavirus in human Merkel cell carcinoma. Science 319:1096–100 [Google Scholar]
  24. Gallo RC, Montagnier L. 1988. AIDS in 1988. Sci. Am. 259:41–48 [Google Scholar]
  25. Hanahan D, Weinberg RA. 2000. The hallmarks of cancer. Cell 100:57–70 [Google Scholar]
  26. Hanahan D, Weinberg RA. 2011. Hallmarks of cancer: the next generation. Cell 144:646–74 [Google Scholar]
  27. Hayward WS, Neel BG, Astrin SM. 1981. Activation of a cellular onc gene by promoter insertion in ALV-induced lymphoid leukosis. Nature 290:475–80 [Google Scholar]
  28. Huebner RJ, Todaro GJ. 1969. Oncogenes of RNA tumor viruses as determinants of cancer. PNAS 64:1087–94 [Google Scholar]
  29. Hunter E. 1997. Viral entry and receptors. See Coffin et al. 1997 71–119
  30. Hunter T. 2009. Tyrosine phosphorylation: thirty years and counting. Curr. Opin. Cell Biol. 21:140–46 [Google Scholar]
  31. Hunter T, Simon J. 2007. A not so brief history of the Oncogene Meeting and its cartoons. Oncogene 26:1260–67 [Google Scholar]
  32. Jacks T. 1990. Translational suppression in gene expression in retroviruses and retrotransposons. Curr. Top. Microbiol. Immunol. 157:93–124 [Google Scholar]
  33. Jamal-Hanjani M, Quezada SA, Larkin J, Swanton C. 2015. Translational implications of tumor heterogeneity. Clin. Cancer Res. 21:1258–66 [Google Scholar]
  34. Kanekiyo M, Bu W, Joyce MG, Meng G, Whittle JR. et al. 2015. Rational design of an Epstein-Barr virus vaccine targeting the receptor-binding site. Cell 162:1090–100 [Google Scholar]
  35. Kirnbauer R, Booy F, Cheng N, Lowy DR, Schiller JT. 1992. Papillomavirus L1 major capsid protein self-assembles into virus-like particles that are highly immunogenic. PNAS 89:12180–84 [Google Scholar]
  36. Kozak M, Shatkin AJ. 1979. Characterization of translational initiation regions from eukaryotic messenger RNAs. Methods Enzymol 60:360–75 [Google Scholar]
  37. Lamarre D, Anderson PC, Bailey M, Beaulieu P, Bolger G. et al. 2003. An NS3 protease inhibitor with antiviral effects in humans infected with hepatitis C virus. Nature 426:186–89 [Google Scholar]
  38. Lander ES, Linton LM, Birren B, Nusbaum C, Zody MC. et al. 2001. Initial sequencing and analysis of the human genome. Nature 409:860–921 [Google Scholar]
  39. Lohmann V, Korner F, Koch J, Herian U, Theilmann L, Bartenschlager R. 1999. Replication of subgenomic hepatitis C virus RNAs in a hepatoma cell line. Science 285:110–13 [Google Scholar]
  40. Martin GS. 1970. Rous sarcoma virus: a function required for the maintenance of the transformed state. Nature 227:1021–23 [Google Scholar]
  41. Miles BD, Robinson HL. 1985. High-frequency transduction of c-erbB in avian leukosis virus-induced erythroblastosis. J. Virol. 54:295–303 [Google Scholar]
  42. Natl. Acad. Med. 2011. Toward Precision Medicine: Building a Knowledge Network for Biomedical Research and a New Taxonomy of Disease Washington, DC: Natl. Acad. Sci. Eng. Med. [Google Scholar]
  43. Nowell PC, Hungerford DA. 1961. Chromosome studies in human leukemia. II. Chronic granulocytic leukemia. J. Natl. Cancer Inst. 27:1013–35 [Google Scholar]
  44. Nusse R, Varmus HE. 1982. Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109 [Google Scholar]
  45. Parada LF, Tabin CJ, Shih C, Weinberg RA. 1982. Human EJ bladder carcinoma oncogene is homologue of Harvey sarcoma virus ras gene. Nature 297:474–78 [Google Scholar]
  46. Parker RC, Varmus HE, Bishop JM. 1981. Cellular homologue (c-src) of the transforming gene of Rous sarcoma virus: isolation, mapping, and transcriptional analysis of c-src and flanking regions. PNAS 78:5842–46 [Google Scholar]
  47. Pastan I, Macchia V. 1967. Mechanism of thyroid-stimulating hormone action. Studies with dibutyl 3′,5′-adenosine monophosphate and lecithinase C. J. Biol. Chem. 242:5757–61 [Google Scholar]
  48. Pastan I, Perlman RL. 1968. The role of the lac promotor locus in the regulation of β-galactosidase synthesis by cyclic 3′,5′-adenosine monophosphate. PNAS 61:1336–42 [Google Scholar]
  49. Paul WE. 2014. Endless fascination. Annu. Rev. Immunol. 32:1–24 [Google Scholar]
  50. Payne GS, Bishop JM, Varmus HE. 1982. Multiple arrangements of viral DNA and an activated host oncogene in bursal lymphomas. Nature 295:209–14 [Google Scholar]
  51. Potter M, Boyce CR. 1962. Induction of plasma-cell neoplasms in strain BALB/c mice with mineral oil and mineral oil adjuvants. Nature 193:1086–87 [Google Scholar]
  52. Prager EM, Brush AH, Nolan RA, Nakanishi M, Wilson AC. 1974. Slow evolution of transferrin and albumin in birds according to micro-complement fixation analysis. J. Mol. Evol. 3:243–62 [Google Scholar]
  53. Rabson AB, Graves BJ. 1997. Synthesis and processing of viral RNA. See Coffin et al. 1997 205–61
  54. Rosenberg N, Jolicoeur P. 1997. Retroviral pathogenesis. See Coffin et al. 1997 475–585
  55. Rowley JD. 1973. Letter: A new consistent chromosomal abnormality in chronic myelogenous leukaemia identified by quinacrine fluorescence and Giemsa staining. Nature 243:290–93 [Google Scholar]
  56. Scholl C, Frohling S, Dunn IF, Schinzel AC, Barbie DA. et al. 2009. Synthetic lethal interaction between oncogenic KRAS dependency and STK33 suppression in human cancer cells. Cell 137:821–34 [Google Scholar]
  57. Shakespeare W. 1623 (1997). Hamlet. The Norton Shakespeare S Greenblatt, W Cohen, JE Howard, KE Mauss New York: Norton [Google Scholar]
  58. Shimizu K, Goldfarb M, Suard Y, Perucho M, Li Y. et al. 1983. Three human transforming genes are related to the viral ras oncogenes. PNAS 80:2112–16 [Google Scholar]
  59. Slamon DJ, Leyland-Jones B, Shak S, Fuchs H, Paton V. et al. 2001. Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N. Engl. J. Med. 344:783–92 [Google Scholar]
  60. Soragni A, Janzen DM, Johnson LM, Lindgren AG, Thai-Quynh Nguyen A. et al. 2016. A designed inhibitor of p53 aggregation rescues p53 tumor suppression in ovarian carcinomas. Cancer Cell 29:90–103 [Google Scholar]
  61. Spector DH, Varmus HE, Bishop JM. 1978. Nucleotide sequences related to the transforming gene of avian sarcoma virus are present in DNA of uninfected vertebrates. PNAS 75:4102–6 [Google Scholar]
  62. Stehelin D, Guntaka RV, Varmus HE, Bishop JM. 1976a. Purification of DNA complementary to nucleotide sequences required for neoplastic transformation of fibroblasts by avian sarcoma viruses. J. Mol. Biol. 101:349–65 [Google Scholar]
  63. Stehelin D, Varmus HE, Bishop JM, Vogt PK. 1976b. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature 260:170–73 [Google Scholar]
  64. Stent GS. 1972. Prematurity and uniqueness in scientific discovery. Sci. Am. 227:84–93 [Google Scholar]
  65. Swanstrom R, Wills JW. 1997. Synthesis, assembly, and processing of viral proteins. See Coffin et al. 1997 263–334
  66. Taparowsky E, Suard Y, Fasano O, Shimizu K, Goldfarb M, Wigler M. 1982. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature 300:762–65 [Google Scholar]
  67. Temin H. 1975. Nobel Lecture: The DNA Provirus Hypothesis Stockholm: Nobel Media [Google Scholar]
  68. Temin HM, Mizutani S. 1970. RNA-dependent DNA polymerase in virions of Rous sarcoma virus. Nature 226:1211–13 [Google Scholar]
  69. Tooze J. 1980. DNA Tumor Viruses Woodbury, NY: Cold Spring Harb. Lab. Press [Google Scholar]
  70. Tooze J. 1981. DNA Tumor Viruses Woodbury, NY: Cold Spring Harb. Lab. Press, 2nd ed.. [Google Scholar]
  71. Unni AM, Lockwood WW, Zejnullahu K, Lee-Lin SQ, Varmus H. 2015. Evidence that synthetic lethality underlies the mutual exclusivity of oncogenic KRAS and EGFR mutations in lung adenocarcinoma. eLife 4:e06907 [Google Scholar]
  72. Varmus H. 1984. The molecular genetics of cellular oncogenes. Annu. Rev. Genet. 18:553–612 [Google Scholar]
  73. Varmus H. 2009. The Art and Politics of Science New York: Norton [Google Scholar]
  74. Varmus H, Levine AJ. 1983. Selected Readings in Tumor Virology Woodbury, NY: Cold Spring Harb. Lab. Press [Google Scholar]
  75. Varmus HE, Perlman RL, Pastan I. 1970. Regulation of lac messenger ribonucleic acid synthesis by cyclic adenosine 3′-5′ monophosphate and glucose. J. Biol. Chem. 245:2259–68 [Google Scholar]
  76. Varmus H, Trimble EL. 2011. Integrating cancer control into global health. Sci. Transl. Med. 3:34–36 [Google Scholar]
  77. Varmus H, Weinberg RA. 1992. Genes and the Biology of Cancer New York: Sci. Am. Libr. [Google Scholar]
  78. Vinograd J, Lebowitz J. 1966. Physical and topological properties of circular DNA. J. Gen. Physiol. 49:103–25 [Google Scholar]
  79. Vogt PK. 1971. Spontaneous segregation of nontransforming viruses from cloned sarcoma viruses. Virology 46:939–46 [Google Scholar]
  80. Vogt PK. 1997. Historical introduction to the general properties of retroviruses. See Coffin et al. 1997 1–25
  81. Weinberg RA. 2007a. The Biology of Cancer New York: Garland Sci. [Google Scholar]
  82. Weinberg RA. 2007b. Tumor suppressor genes. The Biology of Cancer231–74 New York: Garland Sci. [Google Scholar]
  83. Weiss R, Teich N, Varmus H, Coffin J. 1982. RNA Tumor Viruses Woodbury, NY: Cold Spring Harb. Lab. Press [Google Scholar]
  84. Weiss R, Teich N, Varmus H, Coffin J. 1985. RNA Tumor Viruses Woodbury, NY: Cold Spring Harbor Lab. Press, 2nd ed.. [Google Scholar]
  85. Whyte P, Buchkovich KJ, Horowitz JM, Friend SH, Raybuck M. et al. 1988. Association between an oncogene and an anti-oncogene: The adenovirus E1A proteins bind to the retinoblastoma gene product. Nature 334:124–29 [Google Scholar]

Data & Media loading...

  • Article Type: Review Article
This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error