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Cancer Drug Discovery pp 155–174Cite as

Hormonal Anticancer Drugs

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Abstract

Paul Ehrlich, a pioneer in chemotherapy, experienced many failures while developing anticancer chemotherapy due to the indiscriminate toxicity of chemotherapy drugs. In 1915, based on his experience, he stressed on the importance of understanding the biological difference between normal cells and cancer cells for the development of a cancer-specific magic bullet. This suggestion was realized with the invention of targeted anticancer agents after decades of basic research in the field of cancer biology. Another example of an anticancer drug that was successfully developed after understanding the biological characteristics of a specific cancer is the hormonal anticancer drug.

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References

  1. White WJ (1892) Surgical removal of the hypertrophied prostate. Ann Surg 17:70–75

    Google Scholar 

  2. Huggins CB, Masina MH, Eichelberger L, Wharton JD (1939) Quantitative studies of prostatic secretion: I. Characteristics of the normal secretion; the influence of thyroid, suprarenal, and testis extirpation and androgen substitution on the prostatic output. J Exp Med 70:543–556

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Huggins CB, Clark PJ (1940) Quantitative studies of prostatic secretion: II. The effect of castration and of estrogen injection on the hyperplastic prostate glands of dogs. J Exp Med 72:747–762

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Huggins C, Hodges CV (1941) Studies on prostatic cancer: I. The effect of castration, of estrogen and of androgen injection on serum phosphatases in metastatic carcinoma of the prostate. Cancer Res 1:293–297

    CAS  Google Scholar 

  5. Huggins C, Stephens RC, Hodges CV (1941) Studies on prostatic cancer: II. The effects of castration on advanced carcinoma of the prostate gland. Arch Surg 43:209–223

    Article  CAS  Google Scholar 

  6. Schally AV, Kastin AJ, Arimura A (1971) Hypothalamic FSH and LH-regulating hormone. Structure, physiology and clinical studies. Fertil Steril 22:703–721

    Article  CAS  PubMed  Google Scholar 

  7. Schally AV, Arimura A, Kastin AJ, Matsuo H, Baba Y et al (1971) The gonadotropin-releasing hormone: one polypeptide regulates the secretion of luteinizing and follicle stimulating hormones. Science 173:1036–1038

    Article  CAS  PubMed  Google Scholar 

  8. Schally AV, Kastin AJ, Coy DH, Edward T (1976) Tyler Prize Oration – LH releasing hormone and its analogues: recent basic and clinical investigations. Internat Fertil 21:1–30

    CAS  Google Scholar 

  9. Vilchez-Martinez JA, Pedroza E, Arimura A, Schally AV (1979) Paradoxical effects of D-Trp6-luteinizing hormone-releasing hormone on the hypothalamic-pituitary-gonadal axis in immature female rats. Fertil Steril 31:677–682

    Article  CAS  PubMed  Google Scholar 

  10. Redding TW, Schally AV (1981) Inhibition of prostate tumour growth in two rat models by chronic administration of D-Trp6-LH-RH. Proc Natl Acad Sci 78:6509–6512

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Tolis G, Ackman D, Stellos A et al (1982) Tumor growth inhibition in patients with prostatic carcinoma treated with luteinizing hormone-releasing hormone agonists. Proc Natl Acad Sci 79:1658–1662

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anderson KM, Liao S (1968) Selective retention of dihydrotestosterone by prostatic nuclei. Nature 219:277–279

    Article  CAS  PubMed  Google Scholar 

  13. Neri RO, Monahan M (1972) Effects of novel nonsteroidal antiandrogen in canine prostatic hyperplasia. Invest Urol 10:123

    CAS  PubMed  Google Scholar 

  14. Liao S, Howell DK, Chang TM (1974) Action of a nonsteroidal antiandrogen, flutamide, on the receptor binding and nuclear retention of 5 a-dihydrotestosterone in rat ventral prostate. Endocrinology 94:1205–1209

    Article  CAS  PubMed  Google Scholar 

  15. Jung ME, Ouk S, Yoo D, Sawyers CL, Chen C, Tran C, Wongvipat J (2010) Structure-activity relationship for thiohydantoin androgen receptor antagonists for castration resistant prostate cancer. J Med Chem 53:2779–2796

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Tran C, Ouk S, Clegg NJ, Chen Y, Watson PA et al (2009) Development of a second-generation antiandrogen for treatment of advanced prostate cancer. Science 324:787–790

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Scher HI, Beer TM, Higano CS et al (2010) Antitumour activity of MDV3100 in castration-resistant prostate cancer: a phase 1–2 study. Lancet 375:1437–1446

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Scher HI, Fizazi K, Saad F et al (2012) Increased survival with enzalutamide in prostate cancer after chemotherapy. N Engl J Med 367:1187–1197

    Article  CAS  PubMed  Google Scholar 

  19. Heeres J, Backx LJ, Mostmans JH, Van Cutsem J (1979) Antimycotic imidazoles. Part 4. Synthesis and antifungal activity of ketoconazole, a new potent orally active broad-spectrum antifungal agent. J Med Chem 22:1003–1005

    Article  CAS  PubMed  Google Scholar 

  20. Pont A, Williams PL, Azhar S, Reitz RE, Bochra C, Smith ER, Stevens DA (1982) Ketoconazole blocks testosterone synthesis. Arch Intern Med 142:2137–2140

    Article  CAS  PubMed  Google Scholar 

  21. Trachtenberg J, Halpern N, Pont A (1983) Ketoconazole: a novel and rapid treatment for advanced prostatic cancer. J Urol 130:152–153

    CAS  PubMed  Google Scholar 

  22. Loose DS, Kan PB, Hirst MA, Marcus RA, Feldman D (1983) Ketoconazole blocks adrenal steroidogenesis by inhibiting cytochrome P450-dependent enzymes. J Clin Invest 71:1495–1499

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Barrie SE, Potter GA, Goddard PM, Haynes BP, Dowsett M, Jarman M (1994) Pharmacology of novel steroidal inhibitors of cytochrome P45017a (17a-hydroxylase/C17-20 lyase). J Steroid Biochem Mol Biol 50:267–273

    Article  CAS  PubMed  Google Scholar 

  24. Fizazi K et al (2012) Abiraterone acetate for treatment of metastatic castration-resistant prostate cancer: final overall survival analysis of the COU-AA-301 randomised, double-blind, placebo-controlled phase 3 study. Lancet Oncol 13:983–992

    Article  CAS  PubMed  Google Scholar 

  25. Beatson CT (1896) On treatment of inoperable cases of carcinoma of the mamma: suggestions for a new method of treatment with illustrative cases. Lancet 2:162–165

    Article  Google Scholar 

  26. Boyd S (1900) On oophorectomy in cancer of the breast. BMJ 2:1161–1167

    Article  Google Scholar 

  27. Allen E, Doisy EA (1923) An ovarian hormone: preliminary reports on its localization, extraction and partial purification and action in test animals. JAMA 81:810–821

    Google Scholar 

  28. Lacassagne A (1936) Hormonal pathogenesis of adenocarcinoma of the breast. Am J Cancer 27:217–225

    Article  Google Scholar 

  29. Jensen EV, Jacobson HI (1962) Basic guides to the mechanism of estrogen action. Recent Prog Horm Res 18:387–414

    CAS  Google Scholar 

  30. Jensen EV et al (1968) A two-step mechanism for the interaction of estradiol with rat uterus. Proc Natl Acad Sci 59:632–638

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Jensen EV, Block GE, Smith S, Kyser K, DeSombre ER (1971) Estrogen receptors and breast cancer response to adrenalectomy. Natl Cancer Inst Monogr 34:55–70

    CAS  PubMed  Google Scholar 

  32. Harper MJ, Walpole AL (1967) A new derivative of triphenylethylene: effect on implantation and mode of action in rats. J Reprod Fertil 13:101–119

    Article  CAS  PubMed  Google Scholar 

  33. Cole MP, Jones CT, Todd ID (1971) A new antioestrogenic agent in late breast cancer. An early clinical appraisal of ICI46474. Br J Cancer 25:270–275

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Jordan VC, Jaspan T (1976) Tamoxifen as an antitumour agent: oestrogen binding as a predictive test for tumour response. J Endocrinol 68:453–460

    Article  CAS  PubMed  Google Scholar 

  35. Fisher B et al (1986) Adjuvant chemotherapy with and without tamoxifen in the treatment of primary breast cancer: 5-year results from the national surgical adjuvant breast and bowel project trial. J Clin Oncol 4:459–471

    CAS  PubMed  Google Scholar 

  36. Fisher B et al (1998) Tamoxifen for prevention of breast cancer: report of the national surgical adjuvant breast and bowel project P-1 Study. J Natl Cancer Inst 90:1371–1388

    Article  CAS  PubMed  Google Scholar 

  37. Jordan VC, Phelps E, Lindgren JU (1987) Effects of antiestrogens on bone in castrated and intact female rats. Breast Cancer Res Treat 10:31–35

    Article  CAS  PubMed  Google Scholar 

  38. Tamoxifen for early breast cancer: an overview of the randomised trials. Early Breast Cancer trialists’ Collaborative Group (1998) Lancet 351:1451–1467

    Google Scholar 

  39. Kallio S, Kangas L, Blanco G, Johansson R, Karjalainen A, Perilä M, Pippo I et al (1986) A new triphenylethylene compound, Fc-1157a. I hormonal effects. Cancer Chemother Pharmacol 17:101–108

    Article  Google Scholar 

  40. Hayes DF, Van Zyl JA, Hacking A, Goedhals L, Bezwoda WR, Mailliard JA et al (1995) Randomized comparison of tamoxifen and two separate doses of toremifene in postmenopausal patients with metastatic breast cancer. J Clin Oncol 13:2556–2566

    CAS  PubMed  Google Scholar 

  41. Vogel CL (1998) Phase II, and III clinical trials of toremifene for metastatic breast cancer. Oncology 12(Suppl 5):9–13

    CAS  PubMed  Google Scholar 

  42. Jones CD, Jevnikar MG, Pike AJ, Peters MK, Black LJ, Thompson AR, Falcone JF, Clemens JA (1984) Structure-activity studies in a series of 3-aroyl-2-arylbenzo[b]thiophene derivatives leading to [6-hydroxy-2-(4-hydroxyphenyl)benzo[b]thien-3-YL] [4-[2-(1-piperidinyl)ethoxy]-phenyl]methanone hydrochloride (LY156758), a remarkably effective estrogen antagonist with only minimal intrinsic estrogenicity. J Med Chem 27:1057–1066

    Article  CAS  PubMed  Google Scholar 

  43. Buzdar AU, Marcus C, Holmes F, Hug V, Hortobagyi G (1988) Phase II evaluation of LYL56758 in metastatic breast cancer. Oncology 45:344–345

    Article  CAS  PubMed  Google Scholar 

  44. Ettinger B, Black DM, Mitlak BH, Knickerbocker RK, Nickelsen T, Genant HK et al (1999) Reduction of vertebral fracture risk in postmenopausal women with osteoporosis treated with raloxifene: results from a 3-year randomized clinical trial. Multiple Outcomes of Raloxifene Evaluation (MORE) Investigators. JAMA 282:637–645

    Article  CAS  PubMed  Google Scholar 

  45. Cauley JA, Norton L, Lippman ME et al (2001) Continued breast cancer risk reduction in postmenopausal women treated with raloxifene: 4-year results from the MORE trial. Multiple outcomes of raloxifene evaluation. Breast Cancer Res Treat 65:125–134

    Article  CAS  PubMed  Google Scholar 

  46. Vogel VG, Costantino JP, Wickerham DL et al (2006) The Study of Tamoxifen and Raloxifene (STAR): report of the National Surgical Adjuvant Breast and Bowel Project P-2 Trial. JAMA 295:2727–2741

    Article  CAS  PubMed  Google Scholar 

  47. Wakeling AE, Bowler J (1988) Biology and mode of action of pure antioestrogens. J Steroid Biochem 30:141–147

    Article  CAS  PubMed  Google Scholar 

  48. Dauvois S, White R, Parker MG (1993) The antiestrogen ICI 182780 disrupts estrogen receptor nucleocytoplasmic shuttling. J Cell Sci 106:1377–1388

    CAS  PubMed  Google Scholar 

  49. Dauvois S, Danielian PS, White R, Antiestrogen PMG, ICI (1992) 164,384 reduces cellular estrogen receptor content by increasing its turnover. Proc Natl Acad Sci 89:4037–4041

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Osborne CK, Pippen J, Jones SE, Parker LM, Ellis M, Come S et al (2002) Double-blind, randomized trial comparing the efficacy and tolerability of fulvestrant versus anastrozole in postmenopausal women with advanced breast cancer progressing on prior endocrine therapy: results of a North American trial. J Clin Oncol 20:3386–3395

    Article  CAS  PubMed  Google Scholar 

  51. Ryan KJ (1959) Biological aromatization of steroids. J Biol Chem 234:268–272

    CAS  PubMed  Google Scholar 

  52. Chen S, Shively JE, Nakajin S, Shinoda M, Hall PF (1986) Amino terminal sequence analysis of human placenta aromatase. Biochem Biophys Res Commun 135:713–719

    Article  CAS  PubMed  Google Scholar 

  53. Evans CT, Ledesma DB, Schulz TZ, Simpson ER, Mendelson CR (1986) Isolation and characterization of a complementary DNA specific for human aromatase-system cytochrome P-450 mRNA. Proc Natl Acad Sci 83:6387–6391

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Dexter RN, Fishman LM, Ney RC, Liddle GW (1967) Inhibition of adrenal corticosteroid synthesis by aminoglutethimide: studies on the mechanism of action. J Clin Endocrinol 27:473–480

    Article  CAS  Google Scholar 

  55. Griffiths CT, Halls TC, Saba Z, Barlow JJ, Nevinny HB (1973) Preliminary trial of aminoglutethimide in breast cancer. Cancer 32:31–37

    Article  CAS  PubMed  Google Scholar 

  56. Thompson EA Jr, Siiteri PK (1974) The involvement of human placental microsomal cytochrome P-450 in aromatization. J Biol Chem 249:5373–5378

    CAS  PubMed  Google Scholar 

  57. Santen RJ, Santner S, Davis B, Veldhuis J, Samojlik E, Ruby E (1978) Aminoglutethimide inhibits extraglandular estrogen production in postmenopausal women with breast carcinoma. J Clin Endocrinol Metab 47:1257–1265

    Article  CAS  PubMed  Google Scholar 

  58. Brodie AM, Schwarzel WC, Brodie HJ (1976) Studies on the mechanism of estrogen biosynthesis in the rat ovary-I. J Steroid Biochem 7:787–793

    Article  CAS  PubMed  Google Scholar 

  59. Brodie AMH, Schwarzel WC, Shaikh A, Brodie HJ (1977) The effect of an aromatase inhibitor, 4-hydroxy-4-androstene-3,17-dione, on estrogen-dependent processes in reproduction and breast cancer. Endocrinology 100:1684–1695

    Article  CAS  PubMed  Google Scholar 

  60. Pérez Carrión R, Alberola Candel V, Calabresi F et al (1994) Comparison of the selective aromatase inhibitor formestane with tamoxifen as first-line hormonal therapy in postmenopausal women with advanced breast cancer. Ann Oncol 5 Suppl 7:S19–S24

    PubMed  Google Scholar 

  61. Steele RE, Mellor LB, Sawyer WK, Wasvary JM, Browne LJ (1987) In vitro and in vivo studies demonstrating potent and selective estrogen inhibition with the nonsteroidal aromatase inhibitor CGS 16949A. Steroids 50:147–161

    Article  CAS  PubMed  Google Scholar 

  62. Demers LM, Lipton A, Harvey HA, Kambic KB, Grossberg H, Brady C, Santen RJ (1993) The efficacy of CGS 20267 in suppressing estrogen biosynthesis in patients with advanced stage breast cancer. J Steroid Biochem Mol Biol 44:687–691

    Article  CAS  PubMed  Google Scholar 

  63. Plourde PV, Dyroff M, Dukes M (1994) Arimidex: a potent and selective fourth-generation aromatase inhibitor. Breast Cancer Res Treat 30:103–111

    Article  CAS  PubMed  Google Scholar 

  64. Buzdar AU, Jones SE, Vogel CE, Wolter J, Plourde P, Webster A (1997) The Arimidex study group, a phase III trial comparing anastrozole (1 and 10 mg), a potent and selective aromatase inhibitor, with advanced breast carcinoma. Cancer 79:730–739

    Article  CAS  PubMed  Google Scholar 

  65. Ingle JN, Johnson PA, Suman VJ et al (1997) A randomized phase II trial of two dosage levels of letrozole as third-line hormonal therapy for women with metastatic breast carcinoma. Cancer 80:218–224

    Article  CAS  PubMed  Google Scholar 

  66. Di Salle E, Ornati G, Giudici D, Lassus M, Evans TR, Coombes RC (1992) Exemestane (FCE24304), a new steroidal aromatase inhibitor. J Stroid Biochem Mol Biol 43:137–143

    Article  Google Scholar 

  67. Paridaens R, Dirix L, Lohrisch C et al (2000) Promising activity and safety of exemestane as first-line hormonal therapy in metastatic breast cancer patients: final results of an EORTC randomised phase II trial. Breast Cancer Res Treat 64:52

    Google Scholar 

  68. Herzog HL, Nobile A, Tolksdorf S et al (1955) New anti-arthritic steroids. Science 121:176

    Article  CAS  PubMed  Google Scholar 

  69. Freireich EJ, Karon M, Frei E III (1964) Quadruple combination therapy (VAMP) for acute lymphocytic leukemia of childhood. Proc Am Assoc Cancer Res 5:20

    Google Scholar 

  70. DeVita VT, Serpick A (1967) Combination chemotherapy in the treatment of advanced Hodgkin’s disease. Proc Am Assoc Cancer Res 8:13

    Google Scholar 

  71. Fried HJ, Thoma RW, Klingsberg A (1953) Oxidation of steroids by microorganisms. III. Side chain degradation, ring D-cleavage and dehydrogenation in ring A. J Am Chem Soc 75:5764–5765

    Article  CAS  Google Scholar 

  72. Segaloff A, Weeth JB, Meyer KK, Rongone EL, Cunningham MEG (1962) Hormonal therapy in cancer of the breast. XIX. The effect of delta 1-testololactone on clinical course and hormonal excretion. Cancer 15:633–635

    Google Scholar 

  73. Goldenberg IS (1969) Clinical trial of Dl-testololactone (NSC 23759), medroxyprogesterone acetate (NSC 26386), and oxylone acetate (NSC 47438) in advanced female mammary cancer. A report of the Cooperative Breast Cancer Group. Cancer 23:109–112

    Google Scholar 

  74. Siiteri PK, Thompson EA (1975) Studies of human placental aromatase. J Steroid Biochem 6:317–320

    Google Scholar 

  75. Ellis B, Kirk DN, Petrow V, Waterhouse B, William DM (1960) Modified steroid hormones. XVII. Some 6-methyl-4,6-dienes. J Chem Soc 2828–2833

    Google Scholar 

  76. Lentz SS, Brady MF, Major FJ, Reid GC, Soper JT (1996) High-dose megestrol acetate in advanced or recurrent endometrial carcinoma: a Gynecologic Oncology Group Study. J Clin Oncol 14:357–361

    Google Scholar 

  77. Alexieva-Figusch J, Blankenstein MA, Hop WCJ, et al. (1984) Treatment of metastatic breast cancer patients with different dosages of megestrol acetate; dose relations, metabolic and endocrine effects. Eur J Cancer Clin Oncol 20:33–40

    Google Scholar 

  78. Brazeau P, Vale W, Burgus R, Ling N, Butcher M, Rivier J, Guillemin R (1973) Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 179:77–79

    Google Scholar 

  79. Bauer W, Briner U, Doepfner W, et al. (1982) SMS 201–995: a very potent and selective octapeptide analog of somatostatin with prolonged action. Life Sci 31:1133–1140

    Google Scholar 

  80. Reichlin S. Somatostatin (1987) Basic and Clinical Status. Plenum Press, New York

    Google Scholar 

  81. Ho KY, Weissberger AJ, Marbach P, Lazarus L (1990) Therapeutic efficacy of the somatostatin analog SMS 201–995 (Octreotide) in acromegaly. Effects of dose and frequency and long term safety. Ann Intern Med 112:173–181

    Google Scholar 

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Authors and Affiliations

  1. College of Pharmacy, Seoul National University, Seoul, Korea (Republic of)

    Kyu-Won Kim & Hee-Jun Wee

  2. Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea (Republic of)

    Jae Kyung Roh

  3. Department of Internal Medicine, CHA Bundang Medical Center, Seongnam, Korea (Republic of)

    Chan Kim

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  1. Kyu-Won Kim
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  4. Chan Kim
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Kim, KW., Roh, J.K., Wee, HJ., Kim, C. (2016). Hormonal Anticancer Drugs. In: Cancer Drug Discovery. Springer, Dordrecht. https://doi.org/10.1007/978-94-024-0844-7_8

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