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Ингибиторы ангиогенеза в терапии эпителиального рака яичников
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Аннотация
Злокачественная опухоль нуждается в активной доставке питательных веществ и кислорода для пролиферации и инвазии, что требует создание новой сети сосудов (неоангиогенез). Нормальный и опухолевый ангиогенез контролируется целым рядом про- и антиангиогенных факторов. VEGF является одним из наиболее мощных стимуляторов неоангиогенеза. У больных раком яичников определяется повышенная концентрация VEGF в плазме и опухолевой ткани. Концентрация VEGF в плазме является независимым негативным прогностическим фактором. VEGF и его рецепторы представляются привлекательной мишенью для целевой терапии у больных раком яичников. Для нейтрализации VEGF в настоящее время используется гуманизированное антитело к нему – бевацизумаб (Авастин).
Ключевые слова: рак яичников, ангиогенез, вазоэндотелиальный фактор роста, бевацизумаб.
Ключевые слова: рак яичников, ангиогенез, вазоэндотелиальный фактор роста, бевацизумаб.
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A malignant tumor needs an active delivery of nutrients and oxygen for proliferation and invasion; it stimulates new vasculature (neoangiogenesis). Some pro- and antiangiogenic factors control a process of the angiogenesis. VEGF is the most powerful neoangiogenesis stimulator. Patients with ovarian cancer have high level of VEGF in the blood and tumor tissue. Level of VEGF is an independent negative prognostic factor. VEGF and receptors are very attractive target for the specific therapy in patients with ovarian cancer. Bevacizumab (Avastin) is humanized monoclonal antibody against VEGF.
Key words: ovarian cancer, angiogenesis, vascular epithelial growth factor, bevacizumab.
Полный текст
Список литературы
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14. Burger RA, Brady MF, Bookman MA et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol 2010; 28: 18s.
15. Perren T, Swart AM, Pfistere J et al. ICON7: a phase III Gynaecologic Cancer InterGroup (GCIS) trial of adding bevacizumab to standard chemotherapy in women with newly diagnosed epithelial ovarian, primary peritoneal or fallopian tube cancer. Ann Oncol 2010; Suppl. 8: 12.
16. Randall LM, Monk BJ. Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 2010; 117: 497–504.
17. Sanjaykumar H, David C, Shenhong W. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol 2009; 10: 559–68.
18. Karlan BY, Oza AM, Hansen VL et al. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients (pts) with recurrent ovarian carcinoma. J Clin Oncol 2010; 28: 390s.
2. Тюляндин С.А., Жуков Н.В. Анти-VEGF-терапия. Клиническая эффективность, возможные механизмы противоопухолевого эффекта и резистентности. Вопр. онкол. 2009; 55 (3): 375–81.
3. Chung AS, Lee J, Ferrara N. Targeting the tumour vasculature: insight from physiological angiogenesis. Nat Rev Cancer 2010; 10: 505–14.
4. Rafii S, Lyden D, Benezra R et al. Vascular and haematopoietic stem cells: novel targets for anti-angiogenesis therapy? Nat Rev Cancer 2002; 2: 826–35.
5. Iliopoulos O, Levy AP, Jiang C et al. Negative regulation of hypoxia-inducible genes by the von Hippel-Lindau protein. Proc Natl Acad Sci USA 1996; 93: 10595–9.
6. Kumaran GC, Jayson GC, Clamp AR. Antiangiogenic drugs in ovarian cancer. Br J Cancer 2009; 100: 1–7.
7. Yap TA, Carden CP, Kaye SB. Beyond chemotherapy: targeted therapies in ovarian cancer. Nat Rev Cancer 2009; 9: 167–81.
8. Monk BJ, Han E, Josephs-Cowan CA et al. Salvage bevacizumab (rhuMAB VEGF)-based therapy after multiple prior cytotoxic regimens in advanced refr- actory epithelial ovarian cancer. Gynecol Oncol 2006; 102: 140–4.
9. Burger RA, Sill MW, Monk BJ et al. Phase II trial of bevacisumab in persistent or recurrent epithelial ovarian cancer or primary peritoneal cancer: a Gynecologic Oncology Group study. J Clin Oncol 2007; 25: 5165–71.
10. Cannistra SA, Matulonis UA, Penson RT et al. Phase II study of bevacizumab in patients with platinum-resistant ovarian cancer or peritoneal serous cancer. J Clin Oncol 2007; 25: 5180–6.
11. Garcia AA, Hirte H, Fleming G et al. Phase II clinical trial of bevacizumab and low- dose metronomic oral cyclophosphamide in recurrent ovarian cancer: a trial of the California, Chicago, and Princess Margaret Hospital phase II consortia. J Clin Oncol 2008; 26: 76–82.
12. Tillmans T, Lowe MP, Schwartzberg LS et al. A phase II study of bevacizumab with nab-paclitaxel in patients with recurrent, platinum-resistant primary epithelial ovarian or primary peritoneal carcinoma. J Clin Oncol 2010; 28: 392s.
13. Micha JP, Goldstein BH, Rettenmaier MA et al. A phast II study of outpatient first-line paclitaxel, carboplatin, and bevacisumab for advanced-stage epithelial ovarian, peritoneal and fallopian tube cancer. Int J Gynecol Cancer 2007; 17: 771–6.
14. Burger RA, Brady MF, Bookman MA et al. Phase III trial of bevacizumab (BEV) in the primary treatment of advanced epithelial ovarian cancer (EOC), primary peritoneal cancer (PPC), or fallopian tube cancer (FTC): A Gynecologic Oncology Group study. J Clin Oncol 2010; 28: 18s.
15. Perren T, Swart AM, Pfistere J et al. ICON7: a phase III Gynaecologic Cancer InterGroup (GCIS) trial of adding bevacizumab to standard chemotherapy in women with newly diagnosed epithelial ovarian, primary peritoneal or fallopian tube cancer. Ann Oncol 2010; Suppl. 8: 12.
16. Randall LM, Monk BJ. Bevacizumab toxicities and their management in ovarian cancer. Gynecol Oncol 2010; 117: 497–504.
17. Sanjaykumar H, David C, Shenhong W. Risk of gastrointestinal perforation in patients with cancer treated with bevacizumab: a meta-analysis. Lancet Oncol 2009; 10: 559–68.
18. Karlan BY, Oza AM, Hansen VL et al. Randomized, double-blind, placebo-controlled phase II study of AMG 386 combined with weekly paclitaxel in patients (pts) with recurrent ovarian carcinoma. J Clin Oncol 2010; 28: 390s.
Авторы
С.А.Тюляндин, А.С.Тюляндина
Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва
Российский онкологический научный центр им. Н.Н.Блохина РАМН, Москва
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S.A. Tjulandin, A.S. Tjulandina
N.N. Blokhin Russian Cancer Research Center, Russian Academy of Medical Science, Moscow
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