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Ангиогенез как мишень для противоопухолевой терапии
Ангиогенез как мишень для противоопухолевой терапии
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Аннотация
Считается, что трансформированная клетка может образовать опухолевую массу только в том случае, если она секретирует факторы роста эндотелия и направленно формирует собственную сосудистую сеть. Процессы сосудообразования в карциномах отличаются от нормального ангиогенеза: вновь образовавшиеся капилляры не обладают правильной структурой и соединяются между собой достаточно случайным образом – это приводит к затруднению кровотока и возникновению отека. Современные антиангиогенные препараты уничтожают подобные неполноценные сосуды и таким образом нормализуют кровоток.
В результате улучшается доставка цитостатических препаратов в опухолевый очаг, а также наблюдается сенситизация трансформированных клеток к лечебным воздействиям. Комбинированное назначение ингибиторов ангиогенеза и химиотерапии сопровождается достоверным улучшением результатов лечения онкологических больных.
Ключевые слова: ангиогенез, противоопухолевая терапия.
Key words: angiogenesis, tumor therapy.
В результате улучшается доставка цитостатических препаратов в опухолевый очаг, а также наблюдается сенситизация трансформированных клеток к лечебным воздействиям. Комбинированное назначение ингибиторов ангиогенеза и химиотерапии сопровождается достоверным улучшением результатов лечения онкологических больных.
Ключевые слова: ангиогенез, противоопухолевая терапия.
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Key words: angiogenesis, tumor therapy.
Полный текст
Список литературы
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18. Huang Y, Goel S, Duda DG et al. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res 2013; 73 (10): 2943–8.
19. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307 (5706): 58–62.
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24. Lambrechts D, Lenz HJ, de Haas S et al. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 2013; 31 (9): 1219–30.
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28. Sirohi B, Philip DS, Shrikhande SV. Regorafenib: carving a niche in the crowded therapeutic landscape. Expert Rev Anticancer Ther 2013; 13 (4): 385–93.
29. Sun W. Angiogenesis in metastatic colorectal cancer and the benefits of targeted therapy. J Hematol Oncol 2012; 5: 63.
30. Suspitsin EN, Kashyap A, Shelekhova KV et al. Evidence for angiogenesis-independent contribution of VEGFR1 (FLT1) in gastric cancer recurrence. Med Oncol 2013; 30 (3): 644.
31. Tabernero J, Van Cutsem E, Lakomý R et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: Prespecified subgroup analyses from the VELOUR trial. Eur J Cancer 2014; 50 (2): 320–31.
32. Takano S. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation. Brain Tumor Pathol 2012; 29 (2): 73–86.
33. Van Cutsem E, Tabernero J, Lakomy R et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30 (28): 3499–506.
34. van Geel RM, Beijnen JH, Schellens JH. Concise drug review: pazopanib and axitinib. Oncologist 2012; 17 (8): 1081–9.
35. Wells SA Jr, Gosnell JE, Gagel RF et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 2010; 28 (5): 767–72.
36. Welti J, Loges S, Dimmeler S, Carmeliet P. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest 2013; 123 (8): 3190–200.
2. Bellou S, Pentheroudakis G, Murphy C, Fotsis T. Anti-angiogenesis in cancer therapy: Hercules and hydra. Cancer Lett. 2013 Sep 28; 338(2): 219-28.
3. Carmeliet P, Jain RK. Molecular mechanisms and clinical applications of angiogenesis. Nature 2011; 473 (7347): 298–307.
4. Cesca M, Bizzaro F, Zucchetti M, Giavazzi R. Tumor Delivery of Chemotherapy Combined with Inhibitors of Angiogenesis and Vascular Targeting Agents. Front Oncol 2013; 3: 259.
5. Chau NG, Haddad RI. Vandetanib for the treatment of medullary thyroid cancer. Clin Cancer Res 20131; 19 (3): 524–9.
6. Custodio A, Barriuso J, de Castro J et al. Molecular markers to predict outcome to antiangiogenic therapies in colorectal cancer: current evidence and future perspectives. Cancer Treat Rev 2013; 39 (8): 908–24.
7. de Gramont A, Van Cutsem E, Schmoll HJ et al. Bevacizumab plus oxaliplatin-based chemotherapy as adjuvant treatment for colon cancer (AVANT): a phase 3 randomised controlled trial. Lancet Oncol 2012; 13 (12): 1225–33.
8. Di Marco V, De Vita F, Koskinas J et al. Sorafenib: from literature to clinical practice. Ann Oncol 2013; 24 (Suppl. 2): ii30–7.
9. Dietvorst MH, Eskens FA. Current and Novel Treatment Options for Metastatic Colorectal Cancer: Emphasis on Aflibercept. Biol Ther 2013; 3: 25–33.
10. Dutcher JP. Recent developments in the treatment of renal cell carcinoma. Ther Adv Urol 2013; 5 (6): 338–53.
11. Folkman J, Merler E, Abernathy C, Williams G. Isolation of a tumor factor responsible for angiogenesis. J Exp Med 1971; 133 (2): 275–88.
12. Gaya A, Tse V. A preclinical and clinical review of aflibercept for the management of cancer. Cancer Treat Rev 2012; 38 (5): 484–93.
13. Giantonio BJ, Catalano PJ, Meropol NJ et al. Eastern Cooperative Oncology Group Study E3200. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J Clin Oncol 2007; 25 (12): 1539–44.
14. Goel S, Wong AH, Jain RK. Vascular normalization as a therapeutic strategy for malignant and nonmalignant disease. Cold Spring Harb Perspect Med 2012; 2 (3): a006486.
15. Gross-Goupil M, François L, Quivy A, Ravaud A. Axitinib: A Review of its Safety and Efficacy in the Treatment of Adults with Advanced Renal Cell Carcinoma. Clin Med Insights Oncol 2013; 7: 269–77.
16. Grothey A, Van Cutsem E, Sobrero A et al. CORRECT Study Group. Regorafenib monotherapy for previously treated metastatic colorectal cancer (CORRECT): an international, multicentre, randomised, placebo-controlled, phase 3 trial. Lancet 2013; 381 (9863): 303–12.
17. Heinrich MC, Maki RG, Corless CL et al. Primary and secondary kinase genotypes correlate with the biological and clinical activity of sunitinib in imatinib-resistant gastrointestinal stromal tumor. J Clin Oncol 2008; 26 (33): 5352–9.
18. Huang Y, Goel S, Duda DG et al. Vascular normalization as an emerging strategy to enhance cancer immunotherapy. Cancer Res 2013; 73 (10): 2943–8.
19. Jain RK. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 2005; 307 (5706): 58–62.
20. Jain RK. Normalizing tumor microenvironment to treat cancer: bench to bedside to biomarkers. J Clin Oncol 2013; 31 (17): 2205–18.
21. Joulain F, Proskorovsky I, Allegra C et al. Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer. Br J Cancer 2013; 109 (7): 1735–43.
22. Kassem MG, Motiur Rahman AF, Korashy HM. Sunitinib malate. Profiles Drug Subst Excip Relat Methodol 2012; 37: 363–88.
23. Lainakis G, Bamias A. Targeting angiogenesis in renal cell carcinoma. Curr Cancer Drug Targets 2008; 8 (5): 349–58.
24. Lambrechts D, Lenz HJ, de Haas S et al. Markers of response for the antiangiogenic agent bevacizumab. J Clin Oncol 2013; 31 (9): 1219–30.
25. Mitchell EP. Targeted therapy for metastatic colorectal cancer: role of aflibercept. Clin Colorectal Cancer 2013; 12 (2): 73–85.
26. Mortimer J, Zonder HB, Pal SK. Lessons learned from the bevacizumab experience. Cancer Control 2012; 19 (4): 309–16.
27. Patel A, Sun W. Ziv-aflibercept in metastatic colorectal cancer. Biologics 2014; 8: 13–25.
28. Sirohi B, Philip DS, Shrikhande SV. Regorafenib: carving a niche in the crowded therapeutic landscape. Expert Rev Anticancer Ther 2013; 13 (4): 385–93.
29. Sun W. Angiogenesis in metastatic colorectal cancer and the benefits of targeted therapy. J Hematol Oncol 2012; 5: 63.
30. Suspitsin EN, Kashyap A, Shelekhova KV et al. Evidence for angiogenesis-independent contribution of VEGFR1 (FLT1) in gastric cancer recurrence. Med Oncol 2013; 30 (3): 644.
31. Tabernero J, Van Cutsem E, Lakomý R et al. Aflibercept versus placebo in combination with fluorouracil, leucovorin and irinotecan in the treatment of previously treated metastatic colorectal cancer: Prespecified subgroup analyses from the VELOUR trial. Eur J Cancer 2014; 50 (2): 320–31.
32. Takano S. Glioblastoma angiogenesis: VEGF resistance solutions and new strategies based on molecular mechanisms of tumor vessel formation. Brain Tumor Pathol 2012; 29 (2): 73–86.
33. Van Cutsem E, Tabernero J, Lakomy R et al. Addition of aflibercept to fluorouracil, leucovorin, and irinotecan improves survival in a phase III randomized trial in patients with metastatic colorectal cancer previously treated with an oxaliplatin-based regimen. J Clin Oncol 2012; 30 (28): 3499–506.
34. van Geel RM, Beijnen JH, Schellens JH. Concise drug review: pazopanib and axitinib. Oncologist 2012; 17 (8): 1081–9.
35. Wells SA Jr, Gosnell JE, Gagel RF et al. Vandetanib for the treatment of patients with locally advanced or metastatic hereditary medullary thyroid cancer. J Clin Oncol 2010; 28 (5): 767–72.
36. Welti J, Loges S, Dimmeler S, Carmeliet P. Recent molecular discoveries in angiogenesis and antiangiogenic therapies in cancer. J Clin Invest 2013; 123 (8): 3190–200.
Авторы
Е.Н.Имянитов
ФГБУ НИИ онкологии им. Н.Н.Петрова Минздрава России, Санкт-Петербург
ФГБУ НИИ онкологии им. Н.Н.Петрова Минздрава России, Санкт-Петербург
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