PROGRESS IN CLINIC TRIALS OF ANTIANGIOGENIC BREAST CANCER THERAPY_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

ZHANG Guofeng , WANG Yuanhe , WANG Qiang.

Department of General Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003;

Corresponding author：

Keywords：

Breast cancer Angiogenesis Angiogenesis inhibitor Neoplasm therapy

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【Abstract】Objective To introduce the progress on clinic trial of antiangiogenic breast cancer therapy.
Methods The current literatures on progress on clinic trial of antiangiogenic breast cancer therapy were reviewed. Results Pathological angiogenesis is a hallmark of cancer. Concentrated efforts in this area of research are leading to the discovery of a growing number of antiangiogenic molecules, more than 30 of which are already on clinical trial. About 10 of angiogenic inhibitors are already on clinical trial of antiangiogenic breast cancer therapy. Most of them are in clinical phase Ⅰ or Ⅱ studies and a few, however, have progressed to phase III evaluation. Some results show that angiogenic inhibitors can reduce the toxicity and be less likely to generate drug resistance than conventional cytotoxic drugs. Conclusion Pathological angiogenesis is indeed essential for breast cancer metastasis and recurrence. Antiangiogenesis can cause regression of the breast cancer and provide a optimum stragy to treat the breast cancer.

Citation： ZHANG Guofeng,WANG Yuanhe,WANG Qiang.. PROGRESS IN CLINIC TRIALS OF ANTIANGIOGENIC BREAST CANCER THERAPY. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2001, 8(5): 358-360. doi: Copy

1.	Weidner N, Semple JP, Welch WR,et al. Tumor angiogenesis and metastasiscorrelation in invasive breast carcinoma 〔Ｊ〕. N Engl J Med，1991; 324(1)∶1.
2.	Goldman E. The growth of malignant disease in man and the lower animals with special reference to the vascular system 〔Ｊ〕. Lancet, 1907; 2(34)∶1236.
3.	Folkman J. Tumor angiogenesis： therapeutic implications 〔Ｊ〕. N Engl J Med, 1971; 285 (21)∶1182.
4.	Kerbel RS. Tumor angiogenesis： past,present and the near future 〔Ｊ〕. Carcinogenesis, 2000; 21(3)∶505.
5.	Peter C, Rakesh KJ. Angiogenesis in cancer and other disease 〔Ｊ〕. Nature, 2000; 407(6802)∶249.
6.	Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis 〔Ｊ〕. Cell, 1996; 86(3)∶353.
7.	Folkman J. Fighting cancer by attacking its blood supply by inlerfering with the expanding network of blood vessel in tumors, researchers hope to cut off the underlying support system 〔Ｊ〕. Sci Am, 1996; 275(2)∶116.
8.	Ramanujan S, Koening GC, Padera T,et al. Local imblance of proangiogenic and antiangiogenic factors: a potential mechanism of focal necrosis and dormancy in tumors 〔Ｊ〕. Cancer Res, 2000; 60(6)∶1442.
9.	Saphir A. Angiogenesis: the unifying concept in cancer 〔Ｊ〕. J Natl Cancer Inst, 1997; 89 (22)∶1658.
10.	Hagedorn M, Bikfalvi A.Target molecules for antiangiogenic therapy： from basic research to clinical trials 〔Ｊ〕. Crit Rev Oncol Hematol, 2000; 34 (2)∶89.
11.	Parkins CS, Holder AL, Hill SA, et al. Determinants of antivascular action by combretastatin A4 phosphate 〔Ｊ〕. Br J Cancer, 2000; 83 (6)∶811.
12.	OReilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth 〔Ｊ〕.Cell, 1997; 88 (2)∶277.
13.	Boehm T, Folkmam J，Browder T,et al. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance 〔Ｊ〕. Nature,1997; 390 (6658)∶404.
14.	Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution 〔Ｊ〕. EMBO J， 1998; 17(6)∶1656.
15.	Sasaki T, Fukai N, Mann K, et al. Structure function and tissue forms of the Cterminal globular domain of collagen XⅧ containing the angiogenesis inhibitor endostatin 〔Ｊ〕. EMBO J， 1998; 17(5)∶4249.
16.	Griscelli F, Li H, Cheong C, et al. Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model 〔Ｊ〕. Proc Natl Acad Sci USA, 2000; 97 (12)∶6698.
17.	Denis LJ, Verweij J. Matrix metalloproteinase inhibitors: present achievements and future prospects 〔Ｊ〕. Invest New Drugs, 1997; 15(3)∶175.
18.	Steward WP. Marimastat (BB2516): current status of development 〔Ｊ〕. Cancer Chemother Pharmacol, 1999; 43(Suppl)∶S56.
19.	Maeshima Y, Colorado PC, Kalluri R. Two RGDindependent alpha v beta 3 integrin binding sites on tumstatin regulate distinct antitumor properties 〔Ｊ〕.J Biol Chem, 2000; 275 (31)∶23745.
20.	Erdreich Epstein A, Shimada H, Groshen S, et al. Integrins alpha(v)beta3 and alpha(v)beta5 are expressed by endothelium of highrisk neuroblastoma and their inhibition is associated with increased endogenous ceramide 〔Ｊ〕.Cancer Res, 2000; 60 (3)∶712.
21.	McMahon G. VEGF receptor signaling in tumor angiogenesis 〔Ｊ〕. Oncologist, 2000; 5 (Suppl)∶3.
22.	Mordenti J, Thomsen K, Liko V, et al. Efficacy and concentrationresponse of murine antiVEGF monoclonal antibody in tumorbearing mice and extrapolation to humans 〔Ｊ〕. Toxicol Pathol, 1999; 27(1)∶14.
23.	Calabrese L, Fleischer AB. Thalidomide： current and potential clinical applications 〔Ｊ〕. Am J Med, 2000; 108 (6)∶487.
24.	Thomposon WD, Li WW, Maragoudakis M. The clinical manipulation of angiogenesis： pathology, sideeffects, surprises, and opportunities with novel human therapies 〔Ｊ〕. J Pathol, 2000; 190 (3)∶330.

1. Weidner N, Semple JP, Welch WR,et al. Tumor angiogenesis and metastasiscorrelation in invasive breast carcinoma 〔Ｊ〕. N Engl J Med，1991; 324(1)∶1.
2. Goldman E. The growth of malignant disease in man and the lower animals with special reference to the vascular system 〔Ｊ〕. Lancet, 1907; 2(34)∶1236.
3. Folkman J. Tumor angiogenesis： therapeutic implications 〔Ｊ〕. N Engl J Med, 1971; 285 (21)∶1182.
4. Kerbel RS. Tumor angiogenesis： past,present and the near future 〔Ｊ〕. Carcinogenesis, 2000; 21(3)∶505.
5. Peter C, Rakesh KJ. Angiogenesis in cancer and other disease 〔Ｊ〕. Nature, 2000; 407(6802)∶249.
6. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis 〔Ｊ〕. Cell, 1996; 86(3)∶353.
7. Folkman J. Fighting cancer by attacking its blood supply by inlerfering with the expanding network of blood vessel in tumors, researchers hope to cut off the underlying support system 〔Ｊ〕. Sci Am, 1996; 275(2)∶116.
8. Ramanujan S, Koening GC, Padera T,et al. Local imblance of proangiogenic and antiangiogenic factors: a potential mechanism of focal necrosis and dormancy in tumors 〔Ｊ〕. Cancer Res, 2000; 60(6)∶1442.
9. Saphir A. Angiogenesis: the unifying concept in cancer 〔Ｊ〕. J Natl Cancer Inst, 1997; 89 (22)∶1658.
10. Hagedorn M, Bikfalvi A.Target molecules for antiangiogenic therapy： from basic research to clinical trials 〔Ｊ〕. Crit Rev Oncol Hematol, 2000; 34 (2)∶89.
11. Parkins CS, Holder AL, Hill SA, et al. Determinants of antivascular action by combretastatin A4 phosphate 〔Ｊ〕. Br J Cancer, 2000; 83 (6)∶811.
12. OReilly MS, Boehm T, Shing Y, et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth 〔Ｊ〕.Cell, 1997; 88 (2)∶277.
13. Boehm T, Folkmam J，Browder T,et al. Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance 〔Ｊ〕. Nature,1997; 390 (6658)∶404.
14. Hohenester E, Sasaki T, Olsen BR, et al. Crystal structure of the angiogenesis inhibitor endostatin at 1.5A resolution 〔Ｊ〕. EMBO J， 1998; 17(6)∶1656.
15. Sasaki T, Fukai N, Mann K, et al. Structure function and tissue forms of the Cterminal globular domain of collagen XⅧ containing the angiogenesis inhibitor endostatin 〔Ｊ〕. EMBO J， 1998; 17(5)∶4249.
16. Griscelli F, Li H, Cheong C, et al. Combined effects of radiotherapy and angiostatin gene therapy in glioma tumor model 〔Ｊ〕. Proc Natl Acad Sci USA, 2000; 97 (12)∶6698.
17. Denis LJ, Verweij J. Matrix metalloproteinase inhibitors: present achievements and future prospects 〔Ｊ〕. Invest New Drugs, 1997; 15(3)∶175.
18. Steward WP. Marimastat (BB2516): current status of development 〔Ｊ〕. Cancer Chemother Pharmacol, 1999; 43(Suppl)∶S56.
19. Maeshima Y, Colorado PC, Kalluri R. Two RGDindependent alpha v beta 3 integrin binding sites on tumstatin regulate distinct antitumor properties 〔Ｊ〕.J Biol Chem, 2000; 275 (31)∶23745.
20. Erdreich Epstein A, Shimada H, Groshen S, et al. Integrins alpha(v)beta3 and alpha(v)beta5 are expressed by endothelium of highrisk neuroblastoma and their inhibition is associated with increased endogenous ceramide 〔Ｊ〕.Cancer Res, 2000; 60 (3)∶712.
21. McMahon G. VEGF receptor signaling in tumor angiogenesis 〔Ｊ〕. Oncologist, 2000; 5 (Suppl)∶3.
22. Mordenti J, Thomsen K, Liko V, et al. Efficacy and concentrationresponse of murine antiVEGF monoclonal antibody in tumorbearing mice and extrapolation to humans 〔Ｊ〕. Toxicol Pathol, 1999; 27(1)∶14.
23. Calabrese L, Fleischer AB. Thalidomide： current and potential clinical applications 〔Ｊ〕. Am J Med, 2000; 108 (6)∶487.
24. Thomposon WD, Li WW, Maragoudakis M. The clinical manipulation of angiogenesis： pathology, sideeffects, surprises, and opportunities with novel human therapies 〔Ｊ〕. J Pathol, 2000; 190 (3)∶330.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

PROGRESS IN CLINIC TRIALS OF ANTIANGIOGENIC BREAST CANCER THERAPY

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