• 四川省醫(yī)學(xué)科學(xué)院 四川省人民醫(yī)院乳腺科（成都，610072）;

【摘要】　 狄諾塞麥?zhǔn)悄壳暗谝粋€(gè)也是唯一獲批的特異性靶向核因子κB受體活化因子配體抑制劑類藥物。在乳腺癌的治療中，無(wú)論是對(duì)于癌癥治療相關(guān)性的骨質(zhì)疏松或者骨轉(zhuǎn)移，狄諾塞麥都能起到很好的治療作用，具有廣闊的應(yīng)用前景。現(xiàn)就狄諾塞麥的藥理特性、治療機(jī)制、臨床試驗(yàn)及效果作一闡述。

引用本文： 羅靜,何宇,周蕾蕾,葉一峰,張曉,庹有林. 狄諾塞麥在乳腺癌中的應(yīng)用. 華西醫(yī)學(xué), 2011, 26(7): 1003-1005. doi: 復(fù)制

1. 　Mercatali L, Ibrahim T, Sacanna E, et al. Bone metastases detection by circulating biomarkers: OPG and rank-L[J]. Int J Oncol, 2011, 39(1): 255-261.
2. 　Boyle WJ, Scott SW, Lacey DL. Osteoclast differentiation and activation[J]. Nature, 2003, 423(6937): 337-342.
3. 　Boyce BF, Hughes DE, Wright KR, et al. Recent advances in bone biologyprovide insight into the pathogenesis of bone diseases[J]. Lab Invest, 1999, 79(2): 83-94.
4. 　Tometsko M, Roudier M, Canon J, et al. Rank-L inhibition causes a greater suppressionof tumor-induced osteoclastogenesis than zoledronate treatment in vivo and rank-L rescues osteoclasts from zoledronate killing in vitro[J]. Am Soc Bone Miner Res, 2006, 21(Suppl 1): Abstract M076.
5. 　Boyce BF, Xing L. Biology of RANK, RANK-L, and osteoprotegerin[J]. Arthritis Res Ther, 2007, 1(Suppl 9): S1.
6. 　田明嫄, 黃安斌. Denosumab在骨破壞性疾病中的應(yīng)用進(jìn)展[J]. 中華風(fēng)濕病學(xué)雜志, 2009, 13(5): 349-352.
7. 　Santini D, Galluzzo S, Zoccoli A, et al. New molecular targets in bone metastases[J]. Cancer Treat Rev, 2010, 36(Suppl 3): S6-S10.
8. 　Reddy GK, Nadler E, Jain VK. Denosumab (AMG 162), a fully human monoclonal antibody against rank ligand activity[J]. Support Cancer Ther, 2005, 3(1): 14-15.
9. 　Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer[J]. J Clin Oncol, 2008, 26(30): 4875-4882.
10. 　Paget S. The distribution of secondary growths in cancer of the breast[J]. Lancet, 1889, 133(3421): 571-573.
11. 　Holstead JD, Nakashima T, Sanchez OH, et al. Regulation of cancer cell migration and bone metastasis by rankl[J]. Nature, 2006, 440(7084): 692-696.
12. 　Vignot S, Khayat D. A step in the journey of denosumab from bone-targeted therapy to seed-and soil-targeted therapy[J]. J Clin Oncol, 2009, 27(10): 1534-1536.
13. 　Roodman GD. Mechanisms of bone metastasis[J]. N Engl J Med, 2004, 350(16): 1655-1664.
14. 　Terpos E, Efstathiou E, Christoulas D, et al. Rankl inhibition:clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases[J]. Expert Opin Biol Ther, 2009, 9(4): 465-479.
15. 　Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappab ligand inhibitor,denosumab,in patients with multiple myeloma or bone metastases from breast cancer[J]. Clin Cancer Res, 2006, 12(4): 1221-1228.
16. 　Yonemori K, Fujiwara Y, Minami H, et al. Phase 1 trial of denosumab safety,pharmacokinetics,and pharmacodynamics in japanese women with breast cancer-related bone metastases[J]. Cancer Sci, 2008, 99(6): 1237-1242.
17. 　Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases[J]. J Clin Oncol, 2007, 25(28): 4431-4437.
18. 　Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer:a randomized,double-blind study[J]. J Clin Oncol, 2010, 28(35): 5132-5139.
19. 　Castellano D, Sepulveda JM, García-escobar I, et al. The role of rank-ligand inhibition in cancer:the story of denosumab[J]. Oncologist, 2011, 16(2): 136-145.
20. 　Scott LJ, Muir VJ. Denosumab:in the prevention of skeletal-related events in patients with bone metastases from solid tumours[J]. Drugs, 2011, 71(8): 1059-1069.
21. 　Barton MK. Denosumab an option for patients with bone metastasis from breast cancer[J]. CA Cancer J Clin, 2011, 61(3): 135-136.
  1. 1. 　Mercatali L, Ibrahim T, Sacanna E, et al. Bone metastases detection by circulating biomarkers: OPG and rank-L[J]. Int J Oncol, 2011, 39(1): 255-261.
  2. 2. 　Boyle WJ, Scott SW, Lacey DL. Osteoclast differentiation and activation[J]. Nature, 2003, 423(6937): 337-342.
  3. 3. 　Boyce BF, Hughes DE, Wright KR, et al. Recent advances in bone biologyprovide insight into the pathogenesis of bone diseases[J]. Lab Invest, 1999, 79(2): 83-94.
  4. 4. 　Tometsko M, Roudier M, Canon J, et al. Rank-L inhibition causes a greater suppressionof tumor-induced osteoclastogenesis than zoledronate treatment in vivo and rank-L rescues osteoclasts from zoledronate killing in vitro[J]. Am Soc Bone Miner Res, 2006, 21(Suppl 1): Abstract M076.
  5. 5. 　Boyce BF, Xing L. Biology of RANK, RANK-L, and osteoprotegerin[J]. Arthritis Res Ther, 2007, 1(Suppl 9): S1.
  6. 6. 　田明嫄, 黃安斌. Denosumab在骨破壞性疾病中的應(yīng)用進(jìn)展[J]. 中華風(fēng)濕病學(xué)雜志, 2009, 13(5): 349-352.
  7. 7. 　Santini D, Galluzzo S, Zoccoli A, et al. New molecular targets in bone metastases[J]. Cancer Treat Rev, 2010, 36(Suppl 3): S6-S10.
  8. 8. 　Reddy GK, Nadler E, Jain VK. Denosumab (AMG 162), a fully human monoclonal antibody against rank ligand activity[J]. Support Cancer Ther, 2005, 3(1): 14-15.
  9. 9. 　Ellis GK, Bone HG, Chlebowski R, et al. Randomized trial of denosumab in patients receiving adjuvant aromatase inhibitors for nonmetastatic breast cancer[J]. J Clin Oncol, 2008, 26(30): 4875-4882.
  10. 10. 　Paget S. The distribution of secondary growths in cancer of the breast[J]. Lancet, 1889, 133(3421): 571-573.
  11. 11. 　Holstead JD, Nakashima T, Sanchez OH, et al. Regulation of cancer cell migration and bone metastasis by rankl[J]. Nature, 2006, 440(7084): 692-696.
  12. 12. 　Vignot S, Khayat D. A step in the journey of denosumab from bone-targeted therapy to seed-and soil-targeted therapy[J]. J Clin Oncol, 2009, 27(10): 1534-1536.
  13. 13. 　Roodman GD. Mechanisms of bone metastasis[J]. N Engl J Med, 2004, 350(16): 1655-1664.
  14. 14. 　Terpos E, Efstathiou E, Christoulas D, et al. Rankl inhibition:clinical implications for the management of patients with multiple myeloma and solid tumors with bone metastases[J]. Expert Opin Biol Ther, 2009, 9(4): 465-479.
  15. 15. 　Body JJ, Facon T, Coleman RE, et al. A study of the biological receptor activator of nuclear factor-kappab ligand inhibitor,denosumab,in patients with multiple myeloma or bone metastases from breast cancer[J]. Clin Cancer Res, 2006, 12(4): 1221-1228.
  16. 16. 　Yonemori K, Fujiwara Y, Minami H, et al. Phase 1 trial of denosumab safety,pharmacokinetics,and pharmacodynamics in japanese women with breast cancer-related bone metastases[J]. Cancer Sci, 2008, 99(6): 1237-1242.
  17. 17. 　Lipton A, Steger GG, Figueroa J, et al. Randomized active-controlled phase II study of denosumab efficacy and safety in patients with breast cancer-related bone metastases[J]. J Clin Oncol, 2007, 25(28): 4431-4437.
  18. 18. 　Stopeck AT, Lipton A, Body JJ, et al. Denosumab compared with zoledronic acid for the treatment of bone metastases in patients with advanced breast cancer:a randomized,double-blind study[J]. J Clin Oncol, 2010, 28(35): 5132-5139.
  19. 19. 　Castellano D, Sepulveda JM, García-escobar I, et al. The role of rank-ligand inhibition in cancer:the story of denosumab[J]. Oncologist, 2011, 16(2): 136-145.
  20. 20. 　Scott LJ, Muir VJ. Denosumab:in the prevention of skeletal-related events in patients with bone metastases from solid tumours[J]. Drugs, 2011, 71(8): 1059-1069.
  21. 21. 　Barton MK. Denosumab an option for patients with bone metastasis from breast cancer[J]. CA Cancer J Clin, 2011, 61(3): 135-136.