Skip to main content
NCBI home page
Postgraduate Medical Journal logoLink to Postgraduate Medical Journal
. 2001 Aug;77(910):492–497. doi: 10.1136/pmj.77.910.492

Familiar drugs may prevent cancer

R Sharma 1, A Gescher 1, K O'Byrne 1, W Steward 1
PMCID: PMC1742095  PMID: 11470927

Abstract

Despite positive results in large scale chemoprevention trials, many physicians are unaware of the potential cancer preventive properties of drugs in common usage. The antioestrogen tamoxifen and the selective cyclo-oxygenase-2 inhibitor celecoxib have been licensed in the USA for the chemoprevention of breast and colorectal cancers respectively in selected high risk individuals. Similarly, folate and retinol have been shown to decrease the incidence of colorectal cancer and squamous cell carcinoma of the skin respectively in large scale intervention trials. Other retinoids have proved efficacious in the tertiary chemoprevention of cancers of the breast and head/neck. Epidemiological evidence also exists in favour of aspirin, non-steroidal anti-inflammatory drugs, and angiotensin converting enzyme inhibitors preventing certain cancers. Phytochemicals may represent less toxic alternatives to these agents. Although some of these drugs are available without prescription and most are not yet licensed for use in cancer chemoprevention, physicians and students of medicine should be aware of this accumulating evidence base. Practitioners should be amenable to patient referral to discuss complex issues such as risk estimation or potential benefit from intervention.


Keywords: cancer chemoprevention; tamoxifen; folate; retinoids; cyclo-oxygenase

Full Text

The Full Text of this article is available as a PDF (125.4 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Arbiser J. L., Klauber N., Rohan R., van Leeuwen R., Huang M. T., Fisher C., Flynn E., Byers H. R. Curcumin is an in vivo inhibitor of angiogenesis. Mol Med. 1998 Jun;4(6):376–383. [PMC free article] [PubMed] [Google Scholar]
  2. Bergman L., Beelen M. L., Gallee M. P., Hollema H., Benraadt J., van Leeuwen F. E. Risk and prognosis of endometrial cancer after tamoxifen for breast cancer. Comprehensive Cancer Centres' ALERT Group. Assessment of Liver and Endometrial cancer Risk following Tamoxifen. Lancet. 2000 Sep 9;356(9233):881–887. doi: 10.1016/s0140-6736(00)02677-5. [DOI] [PubMed] [Google Scholar]
  3. Chen J., Giovannucci E., Hankinson S. E., Ma J., Willett W. C., Spiegelman D., Kelsey K. T., Hunter D. J. A prospective study of methylenetetrahydrofolate reductase and methionine synthase gene polymorphisms, and risk of colorectal adenoma. Carcinogenesis. 1998 Dec;19(12):2129–2132. doi: 10.1093/carcin/19.12.2129. [DOI] [PubMed] [Google Scholar]
  4. Chen J., Giovannucci E., Kelsey K., Rimm E. B., Stampfer M. J., Colditz G. A., Spiegelman D., Willett W. C., Hunter D. J. A methylenetetrahydrofolate reductase polymorphism and the risk of colorectal cancer. Cancer Res. 1996 Nov 1;56(21):4862–4864. [PubMed] [Google Scholar]
  5. Cole M. P., Jones C. T., Todd I. D. A new anti-oestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474. Br J Cancer. 1971 Jun;25(2):270–275. doi: 10.1038/bjc.1971.33. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Collet J. P., Sharpe C., Belzile E., Boivin J. F., Hanley J., Abenhaim L. Colorectal cancer prevention by non-steroidal anti-inflammatory drugs: effects of dosage and timing. Br J Cancer. 1999 Sep;81(1):62–68. doi: 10.1038/sj.bjc.6690651. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Cummings S. R., Eckert S., Krueger K. A., Grady D., Powles T. J., Cauley J. A., Norton L., Nickelsen T., Bjarnason N. H., Morrow M. The effect of raloxifene on risk of breast cancer in postmenopausal women: results from the MORE randomized trial. Multiple Outcomes of Raloxifene Evaluation. JAMA. 1999 Jun 16;281(23):2189–2197. doi: 10.1001/jama.281.23.2189. [DOI] [PubMed] [Google Scholar]
  8. Cuzick J., Baum M. Tamoxifen and contralateral breast cancer. Lancet. 1985 Aug 3;2(8449):282–282. doi: 10.1016/s0140-6736(85)90338-1. [DOI] [PubMed] [Google Scholar]
  9. De Flora S., Balansky R., Scatolini L., Di Marco C., Gasparini L., Orlando M., Izzotti A. Adducts to nuclear DNA and mitochondrial DNA as biomarkers in chemoprevention. IARC Sci Publ. 1996;(139):291–301. [PubMed] [Google Scholar]
  10. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  11. Feinberg A. P., Vogelstein B. Hypomethylation of ras oncogenes in primary human cancers. Biochem Biophys Res Commun. 1983 Feb 28;111(1):47–54. doi: 10.1016/s0006-291x(83)80115-6. [DOI] [PubMed] [Google Scholar]
  12. Ferraroni M., La Vecchia C., D'Avanzo B., Negri E., Franceschi S., Decarli A. Selected micronutrient intake and the risk of colorectal cancer. Br J Cancer. 1994 Dec;70(6):1150–1155. doi: 10.1038/bjc.1994.463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Fisher B., Costantino J. P., Wickerham D. L., Redmond C. K., Kavanah M., Cronin W. M., Vogel V., Robidoux A., Dimitrov N., Atkins J. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998 Sep 16;90(18):1371–1388. doi: 10.1093/jnci/90.18.1371. [DOI] [PubMed] [Google Scholar]
  14. Folkman J. Seminars in Medicine of the Beth Israel Hospital, Boston. Clinical applications of research on angiogenesis. N Engl J Med. 1995 Dec 28;333(26):1757–1763. doi: 10.1056/NEJM199512283332608. [DOI] [PubMed] [Google Scholar]
  15. Forni G., Lollini P. L., Musiani P., Colombo M. P. Immunoprevention of cancer: is the time ripe? Cancer Res. 2000 May 15;60(10):2571–2575. [PubMed] [Google Scholar]
  16. Gail M. H., Brinton L. A., Byar D. P., Corle D. K., Green S. B., Schairer C., Mulvihill J. J. Projecting individualized probabilities of developing breast cancer for white females who are being examined annually. J Natl Cancer Inst. 1989 Dec 20;81(24):1879–1886. doi: 10.1093/jnci/81.24.1879. [DOI] [PubMed] [Google Scholar]
  17. García Rodríguez L. A., Huerta-Alvarez C. Reduced incidence of colorectal adenoma among long-term users of nonsteroidal antiinflammatory drugs: a pooled analysis of published studies and a new population-based study. Epidemiology. 2000 Jul;11(4):376–381. doi: 10.1097/00001648-200007000-00003. [DOI] [PubMed] [Google Scholar]
  18. Gately S., Twardowski P., Stack M. S., Cundiff D. L., Grella D., Castellino F. J., Enghild J., Kwaan H. C., Lee F., Kramer R. A. The mechanism of cancer-mediated conversion of plasminogen to the angiogenesis inhibitor angiostatin. Proc Natl Acad Sci U S A. 1997 Sep 30;94(20):10868–10872. doi: 10.1073/pnas.94.20.10868. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Giardiello F. M., Hamilton S. R., Krush A. J., Piantadosi S., Hylind L. M., Celano P., Booker S. V., Robinson C. R., Offerhaus G. J. Treatment of colonic and rectal adenomas with sulindac in familial adenomatous polyposis. N Engl J Med. 1993 May 6;328(18):1313–1316. doi: 10.1056/NEJM199305063281805. [DOI] [PubMed] [Google Scholar]
  20. Giovannucci E., Rimm E. B., Stampfer M. J., Colditz G. A., Ascherio A., Willett W. C. Aspirin use and the risk for colorectal cancer and adenoma in male health professionals. Ann Intern Med. 1994 Aug 15;121(4):241–246. doi: 10.7326/0003-4819-121-4-199408150-00001. [DOI] [PubMed] [Google Scholar]
  21. Giovannucci E., Stampfer M. J., Colditz G. A., Hunter D. J., Fuchs C., Rosner B. A., Speizer F. E., Willett W. C. Multivitamin use, folate, and colon cancer in women in the Nurses' Health Study. Ann Intern Med. 1998 Oct 1;129(7):517–524. doi: 10.7326/0003-4819-129-7-199810010-00002. [DOI] [PubMed] [Google Scholar]
  22. Goss K. H., Groden J. Biology of the adenomatous polyposis coli tumor suppressor. J Clin Oncol. 2000 May;18(9):1967–1979. doi: 10.1200/JCO.2000.18.9.1967. [DOI] [PubMed] [Google Scholar]
  23. Hansen L. A., Sigman C. C., Andreola F., Ross S. A., Kelloff G. J., De Luca L. M. Retinoids in chemoprevention and differentiation therapy. Carcinogenesis. 2000 Jul;21(7):1271–1279. [PubMed] [Google Scholar]
  24. Henderson B. E., Ross R. K., Pike M. C., Casagrande J. T. Endogenous hormones as a major factor in human cancer. Cancer Res. 1982 Aug;42(8):3232–3239. [PubMed] [Google Scholar]
  25. Hong W. K., Lippman S. M., Itri L. M., Karp D. D., Lee J. S., Byers R. M., Schantz S. P., Kramer A. M., Lotan R., Peters L. J. Prevention of second primary tumors with isotretinoin in squamous-cell carcinoma of the head and neck. N Engl J Med. 1990 Sep 20;323(12):795–801. doi: 10.1056/NEJM199009203231205. [DOI] [PubMed] [Google Scholar]
  26. Huang M. E., Ye Y. C., Chen S. R., Chai J. R., Lu J. X., Zhoa L., Gu L. J., Wang Z. Y. Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia. Blood. 1988 Aug;72(2):567–572. [PubMed] [Google Scholar]
  27. Hulley S., Grady D., Bush T., Furberg C., Herrington D., Riggs B., Vittinghoff E. Randomized trial of estrogen plus progestin for secondary prevention of coronary heart disease in postmenopausal women. Heart and Estrogen/progestin Replacement Study (HERS) Research Group. JAMA. 1998 Aug 19;280(7):605–613. doi: 10.1001/jama.280.7.605. [DOI] [PubMed] [Google Scholar]
  28. Jordan V. C. Tamoxifen: a personal retrospective. Lancet Oncol. 2000 Sep;1(1):43–49. doi: 10.1016/S1470-2045(00)00009-7. [DOI] [PubMed] [Google Scholar]
  29. Langman M. J., Cheng K. K., Gilman E. A., Lancashire R. J. Effect of anti-inflammatory drugs on overall risk of common cancer: case-control study in general practice research database. BMJ. 2000 Jun 17;320(7250):1642–1646. doi: 10.1136/bmj.320.7250.1642. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Lever A. F., Hole D. J., Gillis C. R., McCallum I. R., McInnes G. T., MacKinnon P. L., Meredith P. A., Murray L. S., Reid J. L., Robertson J. W. Do inhibitors of angiotensin-I-converting enzyme protect against risk of cancer? Lancet. 1998 Jul 18;352(9123):179–184. doi: 10.1016/S0140-6736(98)03228-0. [DOI] [PubMed] [Google Scholar]
  31. Lippman S. M., Lee J. J., Sabichi A. L. Cancer chemoprevention: progress and promise. J Natl Cancer Inst. 1998 Oct 21;90(20):1514–1528. doi: 10.1093/jnci/90.20.1514. [DOI] [PubMed] [Google Scholar]
  32. Manson M. M., Gescher A., Hudson E. A., Plummer S. M., Squires M. S., Prigent S. A. Blocking and suppressing mechanisms of chemoprevention by dietary constituents. Toxicol Lett. 2000 Mar 15;112-113:499–505. doi: 10.1016/s0378-4274(99)00211-8. [DOI] [PubMed] [Google Scholar]
  33. Marnett L. J. Aspirin and the potential role of prostaglandins in colon cancer. Cancer Res. 1992 Oct 15;52(20):5575–5589. [PubMed] [Google Scholar]
  34. Moon T. E., Levine N., Cartmel B., Bangert J. L., Rodney S., Dong Q., Peng Y. M., Alberts D. S. Effect of retinol in preventing squamous cell skin cancer in moderate-risk subjects: a randomized, double-blind, controlled trial. Southwest Skin Cancer Prevention Study Group. Cancer Epidemiol Biomarkers Prev. 1997 Nov;6(11):949–956. [PubMed] [Google Scholar]
  35. Muto T., Bussey H. J., Morson B. C. The evolution of cancer of the colon and rectum. Cancer. 1975 Dec;36(6):2251–2270. doi: 10.1002/cncr.2820360944. [DOI] [PubMed] [Google Scholar]
  36. Pastorino U., Infante M., Maioli M., Chiesa G., Buyse M., Firket P., Rosmentz N., Clerici M., Soresi E., Valente M. Adjuvant treatment of stage I lung cancer with high-dose vitamin A. J Clin Oncol. 1993 Jul;11(7):1216–1222. doi: 10.1200/JCO.1993.11.7.1216. [DOI] [PubMed] [Google Scholar]
  37. Plummer S. M., Holloway K. A., Manson M. M., Munks R. J., Kaptein A., Farrow S., Howells L. Inhibition of cyclo-oxygenase 2 expression in colon cells by the chemopreventive agent curcumin involves inhibition of NF-kappaB activation via the NIK/IKK signalling complex. Oncogene. 1999 Oct 28;18(44):6013–6020. doi: 10.1038/sj.onc.1202980. [DOI] [PubMed] [Google Scholar]
  38. Potter J. D. Colorectal cancer: molecules and populations. J Natl Cancer Inst. 1999 Jun 2;91(11):916–932. doi: 10.1093/jnci/91.11.916. [DOI] [PubMed] [Google Scholar]
  39. Powles T., Eeles R., Ashley S., Easton D., Chang J., Dowsett M., Tidy A., Viggers J., Davey J. Interim analysis of the incidence of breast cancer in the Royal Marsden Hospital tamoxifen randomised chemoprevention trial. Lancet. 1998 Jul 11;352(9122):98–101. doi: 10.1016/S0140-6736(98)85012-5. [DOI] [PubMed] [Google Scholar]
  40. Rao C. V., Rivenson A., Simi B., Reddy B. S. Chemoprevention of colon carcinogenesis by dietary curcumin, a naturally occurring plant phenolic compound. Cancer Res. 1995 Jan 15;55(2):259–266. [PubMed] [Google Scholar]
  41. Roderick P. J., Wilkes H. C., Meade T. W. The gastrointestinal toxicity of aspirin: an overview of randomised controlled trials. Br J Clin Pharmacol. 1993 Mar;35(3):219–226. doi: 10.1111/j.1365-2125.1993.tb05689.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Ruffin M. T., 4th, Krishnan K., Rock C. L., Normolle D., Vaerten M. A., Peters-Golden M., Crowell J., Kelloff G., Boland C. R., Brenner D. E. Suppression of human colorectal mucosal prostaglandins: determining the lowest effective aspirin dose. J Natl Cancer Inst. 1997 Aug 6;89(15):1152–1160. doi: 10.1093/jnci/89.15.1152. [DOI] [PubMed] [Google Scholar]
  43. Sharma R. A. Cancer chemoprevention: a clinical reality. J R Soc Med. 2000 Oct;93(10):518–520. doi: 10.1177/014107680009301006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Sharma R. A., Manson M. M., Gescher A., Steward W. P. Colorectal cancer chemoprevention: biochemical targets and clinical development of promising agents. Eur J Cancer. 2001 Jan;37(1):12–22. doi: 10.1016/s0959-8049(00)00326-9. [DOI] [PubMed] [Google Scholar]
  45. Sharma R. A., Manson M. M., Gescher A., Steward W. P. Colorectal cancer chemoprevention: biochemical targets and clinical development of promising agents. Eur J Cancer. 2001 Jan;37(1):12–22. doi: 10.1016/s0959-8049(00)00326-9. [DOI] [PubMed] [Google Scholar]
  46. Sporn M. B., Newton D. L. Chemoprevention of cancer with retinoids. Fed Proc. 1979 Oct;38(11):2528–2534. [PubMed] [Google Scholar]
  47. Sporn M. B., Suh N. Chemoprevention of cancer. Carcinogenesis. 2000 Mar;21(3):525–530. doi: 10.1093/carcin/21.3.525. [DOI] [PubMed] [Google Scholar]
  48. Sporn M. B., Suh N. Chemoprevention of cancer. Carcinogenesis. 2000 Mar;21(3):525–530. doi: 10.1093/carcin/21.3.525. [DOI] [PubMed] [Google Scholar]
  49. Steinbach G., Lynch P. M., Phillips R. K., Wallace M. H., Hawk E., Gordon G. B., Wakabayashi N., Saunders B., Shen Y., Fujimura T. The effect of celecoxib, a cyclooxygenase-2 inhibitor, in familial adenomatous polyposis. N Engl J Med. 2000 Jun 29;342(26):1946–1952. doi: 10.1056/NEJM200006293422603. [DOI] [PubMed] [Google Scholar]
  50. Tattersall M. H., Thomas H. Recent advances: oncology. BMJ. 1999 Feb 13;318(7181):445–448. doi: 10.1136/bmj.318.7181.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Thun M. J., Namboodiri M. M., Heath C. W., Jr Aspirin use and reduced risk of fatal colon cancer. N Engl J Med. 1991 Dec 5;325(23):1593–1596. doi: 10.1056/NEJM199112053252301. [DOI] [PubMed] [Google Scholar]
  52. Veronesi U., De Palo G., Marubini E., Costa A., Formelli F., Mariani L., Decensi A., Camerini T., Del Turco M. R., Di Mauro M. G. Randomized trial of fenretinide to prevent second breast malignancy in women with early breast cancer. J Natl Cancer Inst. 1999 Nov 3;91(21):1847–1856. doi: 10.1093/jnci/91.21.1847. [DOI] [PubMed] [Google Scholar]
  53. Veronesi U., Maisonneuve P., Costa A., Sacchini V., Maltoni C., Robertson C., Rotmensz N., Boyle P. Prevention of breast cancer with tamoxifen: preliminary findings from the Italian randomised trial among hysterectomised women. Italian Tamoxifen Prevention Study. Lancet. 1998 Jul 11;352(9122):93–97. doi: 10.1016/s0140-6736(98)85011-3. [DOI] [PubMed] [Google Scholar]
  54. Volpert O. V., Ward W. F., Lingen M. W., Chesler L., Solt D. B., Johnson M. D., Molteni A., Polverini P. J., Bouck N. P. Captopril inhibits angiogenesis and slows the growth of experimental tumors in rats. J Clin Invest. 1996 Aug 1;98(3):671–679. doi: 10.1172/JCI118838. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Williams A. R., Balasooriya B. A., Day D. W. Polyps and cancer of the large bowel: a necropsy study in Liverpool. Gut. 1982 Oct;23(10):835–842. doi: 10.1136/gut.23.10.835. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Yin M. J., Yamamoto Y., Gaynor R. B. The anti-inflammatory agents aspirin and salicylate inhibit the activity of I(kappa)B kinase-beta. Nature. 1998 Nov 5;396(6706):77–80. doi: 10.1038/23948. [DOI] [PubMed] [Google Scholar]

Articles from Postgraduate Medical Journal are provided here courtesy of BMJ Publishing Group

RESOURCES