Skip to main content

Thank you for visiting You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

The contributions of Santiago Ramón y Cajal to cancer research — 100 years on


In 1906, Santiago Ramón y Cajal received the Nobel Prize for his detailed description of the nervous system. But Cajal (pronounced 'Cahal') worked in many fields and his contributions to cancer research have been overlooked, mainly because his observations were published in Spanish. As we near Cajal's Nobel Prize centennial celebration, we review his histological slides, original drawings and publications that are related to cancer. There is an impressive body of evidence that shows Cajal's interest in tumour biology.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.


All prices are NET prices.

Figure 1
Figure 2: Original cancer-related material kept at the Museum Ramón y Cajal.
Figure 3: Two examples of staining techniques that were applied to tumours by Cajal.
Figure 4: Original drawing by Cajal that illustrates angiogenesis.
Figure 5: The morphology and development of plasma cells.
Figure 6: The interstitial cells of Cajal.


  1. 1

    Bentivoglio, M. Life and Discoveries of Santiago Ramón y Cajal [online], <> (1998).

    Google Scholar 

  2. 2

    Ramón y Cajal, S. Investigaciones Experimentales Sobre la Génesis Inflamatoria y en Especial Sobre la Emigración de los Leucocitos 1–60 (Imprenta de El Diario Católico, Zaragoza, 1880) (in Spanish).

    Google Scholar 

  3. 3

    Ramón y Cajal, S. Notas de laboratorio I. Textura de la fibra muscular en los mamíferos. Boletín del Instituto Médico Valenciano 20, 129–235 (1887) (in Spanish).

    Google Scholar 

  4. 4

    Llinás, R. R. The contribution of Santiago Ramón y Cajal to functional neuroscience. Nature Rev. Neurosci. 4, 77–80 (2003).

    Article  Google Scholar 

  5. 5

    Ramón y Cajal, S. The structure and connexions of neurons [online], <> (1906).

    Google Scholar 

  6. 6

    Ramón y Cajal, S. Estudios Sobre la Degeneración y Regeneración del Sistema Nervioso (N. Moya, Madrid, 1913) (in Spanish).

    Google Scholar 

  7. 7

    Ramón y Cajal, S. in Degeneration and Regeneration of the Nervous System (ed. May, R. M.) (Oxford University Press, 1928).

    Google Scholar 

  8. 8

    Ramón y Cajal, S. Contribución al estudio de las formas involutivas y monstruosas del comabacilo de Koch. La Crónica Médica. Revista Quincenal de Medicina y Cirujía Prácticas 9, 197–204 (1885) (in Spanish).

    Google Scholar 

  9. 9

    Ramón y Cajal, S. Sobre las células gigantes de la lepra y sus relaciones con las colonias del bacilo leproso. Gaceta Sanitaria de Barcelona 11, 378–386 (1890) (in Spanish).

    Google Scholar 

  10. 10

    Ramón y Cajal, S. Manual de Anatomía Patológica General y Fundamentos de Bacteriología 1st edn 164–172 (Imprenta de la Casa Provincial de Caridad, Barcelona, 1890) (in Spanish).

    Google Scholar 

  11. 11

    Ramón y Cajal, S. Manual de Anatomía Patológica General y Fundamentos de Bacteriología 1st edn 185–187 (Imprenta de la Casa Provincial de Caridad, Barcelona, 1890) (in Spanish).

    Google Scholar 

  12. 12

    Ramón y Cajal, S. Diagnóstico histológico de la rabia. Boletín del Instituto de Sueroterapia, Vacunación y Bacteriología Alfonso XIII 1, 3–7 (1905) (in Spanish).

    Google Scholar 

  13. 13

    Ramón y Cajal, S. Estudios sobre el microbio vírgula del cólera y las inoculaciones profilácticas. Tipografía del Hospicio Provincial de Zaragoza 1–108 (1885) (in Spanish).

  14. 14

    Ramón y Cajal, S. Adenoma primitivo del hígado. Revista de Ciencias Médicas de Barcelona 9, 193–198 (1893) (in Spanish).

    Google Scholar 

  15. 15

    Ramón y Cajal, S. Las defensas orgánicas en el epitelioma y carcinoma. Boletín Oficial del Colegio de Médicos de Madrid 1, 20–28 (1896) (in Spanish).

    Google Scholar 

  16. 16

    Ramón y Cajal, S. Estudios histológicos sobre los tumores epiteliales. Revista Trimestral Micrográfica 1, 83–96 (1896) (in Spanish).

    Google Scholar 

  17. 17

    Ramón y Cajal, S. Sobre la existencia en el papiloma y pólipos mucosos de cuerpos semejantes a blastomicetos. Anales de la Sociedad Española de Historia Natural 25, 3–7 (1896) (in Spanish).

    Google Scholar 

  18. 18

    Ramón y Cajal, S. Métodos de coloración de neoplasias. Revista de Ciencias Médicas de Barcelona 22, 1–8 (1896) (in Spanish).

    Google Scholar 

  19. 19

    Ramón y Cajal, S. Estudios histológicos sobre los tumores epiteliales. Revista Trimestral Micrográfica 1, 169–198 (1896) (in Spanish).

    Google Scholar 

  20. 20

    Dean, M., Fojo, T. & Bates, S. Tumour stem cells and drug resistance. Nature Rev. Cancer 5, 275–284 (2005).

    CAS  Article  Google Scholar 

  21. 21

    Mueller, M. M. & Fusenig, N. E. Friends or foes, bipolar effects of the tumour stroma in cancer. Nature Rev. Cancer 4, 839–850 (2004).

    CAS  Article  Google Scholar 

  22. 22

    Hong, S. H., et al. Cyclooxygenase regulates human oropharyngeal carcinomas via the proinflammatory cytokine IL-6: a general role for inflammation? FASEB J. 14, 1499–1507 (2000).

    CAS  Article  Google Scholar 

  23. 23

    Bergers, G. & Benjamin, L. E. Tumorigenesis and the angiogenesis switch. Nature Rev. Cancer 3, 401–410 (2003).

    CAS  Article  Google Scholar 

  24. 24

    Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186 (1971).

    CAS  Article  Google Scholar 

  25. 25

    Yang, J. C., et al. A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N. Engl. J. Med. 349, 427–434 (2003).

    CAS  Article  Google Scholar 

  26. 26

    Martínez, A., et al. Proadrenomedullin NH2-terminal 20 peptide is a potent angiogenic factor, and its inhibition results in reduction of tumor growth. Cancer Res. 64, 6489–6494 (2004).

    Article  Google Scholar 

  27. 27

    Ramón y Cajal, S. & Tello y Muñoz, J. F. Manual de Anatomía Patológica y Nociones de Bacteriología Patológica 9th edn 376 (Tipografía Artística, Madrid, 1930) (in Spanish).

    Google Scholar 

  28. 28

    Yamagiwa, K. & Ichikawa, K. Experimentelle studie über die pathogenese der epithelial geschwülste. Mitteilungen aus der Medicinischen Fakultät der Ka iserli chen Universität Tokyo 15, 295–344 (1915) (in German).

    Google Scholar 

  29. 29

    Russell, W. An address on a characteristic organism of cancer. Br. Med. J. 2, 1356–1360 (1890).

    CAS  Article  Google Scholar 

  30. 30

    Ribatti, D., et al. Tumor vascularity and tryptase-positive mast cells correlate with a poor prognosis in melanoma. Eur. J. Clin. Invest. 33, 420–425 (2003).

    CAS  Article  Google Scholar 

  31. 31

    Starkey, J. R., Crowle, P. K. & Taubenberger, S. Mast cell deficient W/Wv mice exhibit a decrease rate of tumor angiogenesis. Int. J. Cancer 42, 48–52 (1988).

    CAS  Article  Google Scholar 

  32. 32

    Zudaire, E., et al. A cooperative link between tumor cell derived adrenomedullin and mast cell activation in human carcinogenesis. Am. J. Pathol. (in the press).

  33. 33

    Dabbous, M. K., Haney, L., Nicolson, G. L., Eckley, D. & Woodley, D. G. Mast cell modulation of tumor cell proliferation in rat mammary adenocarcinoma 13762NF. Br. J. Cancer 63, 873–878 (1991).

    CAS  Article  Google Scholar 

  34. 34

    Unna, P. G. Über plasmazellen, insbesondere beim Lupus. Monattsschrift für Praktische Dermatologie 12, 296–317 (1891) (in German).

    Google Scholar 

  35. 35

    Ramón y Cajal, S. Quelques antécédents historiques ignorés sur les Plasmazellen. Anat. Anz. 29, 666–673 (1906) (in French).

    Google Scholar 

  36. 36

    Smith, G. R. & Missailidis, S. Cancer, inflammation and the AT1 and AT2 receptors. J. Inflamm. 1, 3 (2004).

    Article  Google Scholar 

  37. 37

    Narayanan, B. A., Narayanan, N. K., Pittman, B. & Reddy, B. S. Regression of mouse prostatic intraepithelial neoplasia by nonsteroidal anti-inflammatory drugs in the transgenic adenocarcinoma mouse prostate model. Clin. Cancer Res. 10, 7727–7737 (2004).

    CAS  Article  Google Scholar 

  38. 38

    Ramón y Cajal, S. Nota sobre el plexo de Auerbach de la rana. Trabajos del Laboratorio de Histologia de la Facultad de Medicina de Barcelona 2, 23–28 (1892) (in Spanish).

    Google Scholar 

  39. 39

    Lecoin, L., Gabella, G. & Le Douarin, N. Origin of the c-kit-positive interstitial cells in the avian bowel. Development 122, 725–733 (1996).

    CAS  PubMed  Google Scholar 

  40. 40

    Kluppel, M., et al. W/kit gene required for interstitial cells of Cajal and for intestinal pacemaker activity. Nature 373, 347–349 (1995).

    Article  Google Scholar 

  41. 41

    Hanani, M., Farrugia, G. & Komuro, T. Intercellular coupling of interstitial cells of Cajal in the digestive tract. Int. Rev. Cytol. 242, 249–282 (2005).

    CAS  Article  Google Scholar 

  42. 42

    Kindblom, L. G., et al. Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am. J. Pathol. 152, 1259–1269 (1998).

    CAS  PubMed  PubMed Central  Google Scholar 

  43. 43

    Heinrich, M. C., et al. Kinase mutations and imatinib response in patients with metastatic gastrointestinal stromal tumor. J. Clin. Oncol. 21, 4342–4349 (2003).

    CAS  Article  Google Scholar 

  44. 44

    Masson, P. Les névromes sympathiques de l'appendicite oblitérante. Lyon Chir. 18, 281–299 (1921) (in French).

    Google Scholar 

  45. 45

    Jabonero, V. Tumor de fibras nerviosas vegetativas. Arch. Med. Exp. 7, 167–195 (1946) (in Spanish).

    Google Scholar 

  46. 46

    del Río-Hortega, P. in The Microscopic Anatomy of Tumors of the Central and Peripheral Nervous System (Charles C. Thomas, Springfield, 1962).

    Google Scholar 

  47. 47

    Ramón y Cajal, S. Recuerdos de Mi Vida. Historia de Mi Labor Científica (Alianza Editorial, Madrid, 1981) (in Spanish); incomplete English translation available in Ramón y Cajal, S. Recollections of My Life 3rd edn (The MIT Press, Cambridge, 1996).

    Google Scholar 

Download references


We gratefully acknowledge F. Cuttitta and J. Mulshine for their critical reading of the manuscript. The authors are supported by the Spanish Ministry of Science and Education and Red CIEN.

Author information



Corresponding author

Correspondence to Alfredo Martínez.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Related links

Related links


National Cancer Institute


oropharyngeal carcinoma


Interleukin 6



The Cajal Institute

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Martínez, A., Marín, V., Junquera, S. et al. The contributions of Santiago Ramón y Cajal to cancer research — 100 years on. Nat Rev Cancer 5, 904–909 (2005).

Download citation

Further reading


Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing