Современные представления о роли инсулиноподобных и вазоэндотелиальных факторов роста в развитии, прогнозе и таргетной терапии рака яичников


Цитировать

Полный текст

Аннотация

Система инсулиноподобных факторов роста (ИФР) посредством своих митогенных и антиапоптотических эффектов играет немаловажную роль в канцерогенезе. При взаимодействии со своим рецептором ИФР активирует Ras- и Akt-сигнальные пути, что приводит к усилению клеточной пролиферации и угнетению апоптоза. Через стимуляцию проангиогенных факторов, в том числе и фактора роста эндотелия сосудов (VEGF - vascular endothelial growth factor), ИФР-сигнальный путь также опосредует процессы неоангиогенеза, необходимые для развития, прогрессирования и метастазирования злокачественных новообразований. Работы последних лет установили связь между ИФР, VEGF и раком яичников. Новые лекарственные препараты таргетной терапии больных карциномой яичника, направленные на подавление компонентов системы ИФР и VEGF, находятся на стадии экспериментальных и клинических исследований. В обзоре литературы представлены результаты изучения роли ИФР и VEGF в развитии, прогнозе и лечении пациенток, страдающих злокачественными новообразованиями яичников.

Об авторах

Ростислав Игоревич Князев

ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России

Email: sluwba@mail.ru
аспирант каф. онкологии ГБОУ ДПО РМАПО 125993, Россия, Москва, ул. Баррикадная, д. 2/1

Ирина Владимировна Поддубная

ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России

д-р мед. наук, проф., чл.-кор. РАН, зав. каф. онкологии ГБОУ ДПО РМАПО 125993, Россия, Москва, ул. Баррикадная, д. 2/1

Владимир Васильевич Баринов

ФГБУ Российский онкологический научный центр им. Н.Н.Блохина Минздрава России

д-р мед. наук, проф., вед. науч. сотр. отд-ния гинекологии ФГБУ РОНЦ им. Н.Н.Блохина 115478, Россия, Москва, Каширское ш., д. 23

Иван Игоревич Бокин

ГБОУ ДПО Российская медицинская академия последипломного образования Минздрава России

канд. мед. наук, ассистент каф. онкологии ГБОУ ДПО РМАПО 125993, Россия, Москва, ул. Баррикадная, д. 2/1

Список литературы

  1. Давыдов М.И., Аксель Е.М. Статистика злокачественных новообразований в России и странах СНГ в 2012 г. М.: РОНЦ им. Н.Н.Блохина, 2014; с. 51-66.
  2. Каприн А.Д., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2013 году (заболеваемость и смертность). М.: МНИОИ им. П.А.Герцена, 2015.
  3. Клиническая онкогинекология: Руководство для врачей. Под ред. В.П.Козаченко. М.: Медицина, 2005.
  4. Хохлова С.В. Роль бевацизумаба в лечении рака яичников. Онкогинекология. 2012; 3: 33-45.
  5. Чиссов В.И., Старинский В.В., Петрова Г.В. Злокачественные новообразования в России в 2011 году (заболеваемость и смертность). М.: МНИОИ им. П.А.Герцена, 2013.
  6. An Y et al. Local expression of insulin - like growth factor-I, insulin - like growth factor-I receptor, and estrogen receptor alpha in ovarian cancer. Oncol Res Treat 2009; 32 (11): 638-44.
  7. Bao B et al. Hypoxia - induced aggressiveness of pancreatic cancer cells is due to increased expression of VEGF, IL-6 and miR-21, which can be attenuated by CDF treatment. PloS one 2012; 7 (12): e50165.
  8. Baxter R.C. IGF binding proteins in cancer: mechanistic and clinical insights. Nature Rev Cancer 2014; 14 (5): 329-41.
  9. Belfiore A, Malaguarnera R. Insulin receptor and cancer. Endocrine - related cancer 2011; 18 (4): R125-R147.
  10. Beltran P.J et al. Ganitumab (AMG 479) Inhibits IGF-II-Dependent Ovarian Cancer Growth and Potentiates Platinum-Based Chemotherapy. Clin Cancer Res 2014; 20 (11): 2947-58.
  11. Brokaw J et al. IGF-I in epithelial ovarian cancer and its role in disease progression. Growth Factors 2007; 25 (5): 346-54.
  12. Bruchim I et al. BRCA1/2 germline mutations in Jewish patients with uterine serous carcinoma. Int J Gynecol Cancer 2010; 20; 7: 1148-53.
  13. Bruchim I, Sarfstein R, Werner H. The IGF hormonal network in endometrial cancer: functions, regulation, and targeting approaches. Frontiers in Endocrinol 2014; 5.
  14. Brustmann H. Vascular endothelial growth factor expression in serous ovarian carcinoma: relationship with topoisomerase IIa and prognosis. Gynecol Oncol 2004; 95 (1): 16-22.
  15. Burger R.A et al. Incorporation of bevacizumab in the primary treatment of ovarian cancer. N Engl J Med 2011; 365 (26): 2473-83.
  16. Cao Y et al. Prediagnostic plasma IGFBP-1, IGF-1 and risk of prostate cancer. Int J Cancer 2015; 136 (10): 2418-26.
  17. Chakraborty A.K, Welsh A, Di Giovanna M.P. Co - targeting the insulin - like growth factor I receptor enhances growth - inhibitory and pro - apoptotic effects of anti - estrogens in human breast cancer cell lines. Breast Cancer Res Treat 2010; 120 (20): 327-35.
  18. Chen H et al. Correlation of the expressions of VEGF-C and VEGFR-3 to the pathological grade of prostate cancer. Nan fang yi ke da xue xue bao. J South Med Univ 2011; 31 (1): 155-9.
  19. Cheng D, Liang B, Li Y. Serum vascular endothelial growth factor (VEGF-C) as a diagnostic and prognostic marker in patients with ovarian cancer. PloS One 2013; 8 (2): e55309.
  20. Crociani O et al. hERG1 channels regulate VEGF-A secretion in human gastric cancer: clinicopathological correlations and therapeutical implications. Clin Cancer Res 2014; 20 (6): 1502-12.
  21. Evans T et al. Phase I dose - escalation study of continuous oral dosing of OSI-906, a dual tyrosine kinase inhibitor of insulin - like growth factor-1 receptor (IGF-1R) and insulin receptor (IR), in patients with advanced solid tumors. ASCO Meeting Abstracts 2010; 28: 2531.
  22. Flannery C.A et al. SAT-0017: Differential Expression of IR-a, IR-B and IGF-1R in Endometrium Reflects Physiology during the Menstrual Cycle and Demonstrates a Distinct Expression Signature in Endometrial Adenocarcinoma. 2014.
  23. Gadducci A et al. Vascular endothelial growth factor (VEGF) expression in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma. Anticancer Res 2002; 23 (3C): 3001-8.
  24. Gao J et al. Targeting the insulin - like growth factor axis for the development of novel therapeutics in oncology. Cancer Res 2012; 72 (10): 3-12.
  25. Garcı́a-Echeverrı́a C et al. In vivo antitumor activity of NVP-AEW541 - a novel, potent, and selective inhibitor of the IGF-IR kinase. Cancer Cell 2004; 5 (3): 231-9.
  26. Gotlieb W.H et al. Intravenous aflibercept for treatment of recurrent symptomatic malignant ascites in patients with advanced ovarian cancer: a phase 2, randomised, double - blind, placebo - controlled study. Lancet Oncol 2012; 13 (20): 154-62.
  27. Guleria S, Sharma J, Kaushik S. Laron syndrome. J Postgraduate Med 2014; 60 (3): 322.
  28. Gungor A et al. FRI-319: Hypoinsulinemic Hypoglycemia Secondary to Solitary Fibrous Tumor of the Pleura: Doege-Potter Syndrome; A Case Report 2015.
  29. Haluska P et al. Phase I dose - escalation study of MEDI-573, a bispecific, antiligand monoclonal antibody against IGFI and IGFII, in patients with advanced solid tumors. Clin Cancer Res 2014; 20 (18): 4747-57.
  30. Harb W.A et al. Final results of a phase I study evaluating the combination of linsitinib, a dual inhibitor of insulin - like growth factor-1 receptor (IGF-1R), and insulin receptor (IR) with weekly paclitaxel (PAC) in patients (Pts) with advanced solid tumors. J Clin Oncol 2013; 31 (15).
  31. He L, He J, Zhao X. Expression of VEGF-D in epithelial ovarian cancer and its relationship to lymphatic metastasis. Asia-Pacific J Clin Oncol 2013.
  32. Herr D et al. VEGF induces ascites in ovarian cancer patients via increasing peritoneal permeability by downregulation of Claudin 5. Gynecol Oncol 2012; 127 (1): 210-6.
  33. Hormones T.E, Group B.C.C. Insulin - like growth factor 1 (IGF1), IGF binding protein 3 (IGFBP3), and breast cancer risk: pooled individual data analysis of 17 prospective studies. Lancet Oncol 2010; 11 (6): 530-42.
  34. Huang Y.F et al. Circulating IGF system and treatment outcome in epithelial ovarian cancer. Endocrine - related cancer 2014; 21 (2): 217-29.
  35. Ioannou N et al. Treatment with a combination of the ErbB (HER) family blocker afatinib and the IGF-IR inhibitor, NVP-AEW541 induces synergistic growth inhibition of human pancreatic cancer cells. BMC cancer 2013; 13 (1): 41.
  36. Kauppinen-Mäkelin R et al. Increased cancer incidence in acromegaly - a nationwide survey. Clin Endocrinol 2010; 72 (2): 278-9.
  37. Khromova N et al. Downregulation of VEGF-C expression in lung and colon cancer cells decelerates tumor growth and inhibits metastasis via multiple mechanisms. Oncogene 2011; 31 (11): 1389-97.
  38. Liang B et al. Elevated VEGF concentrations in ascites and serum predict adverse prognosis in ovarian cancer. Scan J Clin Lab Investiga 2013; 73 (4): 309-14.
  39. Lu L et al. The relationship of insulin - like growth factor-II, insulin - like growth factor binding protein-3, and estrogen receptor - alpha expression to disease progression in epithelial ovarian cancer. Clin Cancer Res 2006; 12 (4): 1208-14.
  40. Ludovini V et al. Concomitant high gene copy number and protein overexpression of IGF1R and EGFR negatively affect disease - free survival of surgically resected non - small - cell - lung cancer patients. Cancer Chemother Pharmacol 2013; 71 (3): 671-80.
  41. Mikami K et al. Prostate cancer risk in relation to insulin - like growth factor (IGF)-I and IGF-binding protein-3: A nested case - control study in large scale cohort study in Japan. Asian Pacific J Cancer Prevent: APJCP 2009; 10: 57-61.
  42. Molife L.R et al. The insulin - like growth factor-I receptor inhibitor figitumumab (CP-751,871) in combination with docetaxel in patients with advanced solid tumours: results of a phase Ib dose - escalation, open - label study. Br J Cancer 2010; 103 (3): 332-9.
  43. Moroney J.W, Sood A.K, Coleman R.L. Aflibercept in epithelial ovarian carcinoma. Future Oncology 2009; 5 (5): 591-600.
  44. Nakazawa Y et al. A multi - targeting strategy using lenvatinib and golvatinib: Maximizing its anti - angiogenesis activity in preclinical cancer model. Cancer Sci 2014.
  45. National cancer institute. Surveillance, epidemiology, and end results program. http://seer.cancer.gov/statfacts/html/ovary.html
  46. Park J.H et al. Matrix metalloproteinase 9 promotes breast cancer through regulation of insulin - like growth factor - binding proteins. Cancer Res 2012; 72 (8 Suppl.): 2465.
  47. Pengchong H, Tao H. Expression of IGF-1R, VEGF-C and D2-40 and their correlation with lymph node metastasis in endometrial adenocarcinoma. Eur J Gynaecol Oncol 2010; 32 (6): 660-4.
  48. Reinhardt H.C, Schumacher B. The p53 network: cellular and systemic DNA damage responses in aging and cancer. Trends in Genetics 2012; 28 (3): 128-36.
  49. Rinaldi S et al. Serum levels of IGF-I, IGFBP-3 and colorectal cancer risk: results from the EPIC cohort, plus a meta - analysis of prospective studies. Int J Cancer 2010; 126 (7): 1702-15.
  50. Salvesen H.B, Haldorsen I.S, Trovik J. Markers for individualised therapy in endometrial carcinoma. Lancet Oncol 2012; 13 (8): e353-e361.
  51. Samani A.A et al. The role of the IGF system in cancer growth and metastasis: overview and recent insights. Endocrine Rev 2007; 28 (1): 20-47.
  52. Sayer R.A et al. High insulin - like growth factor-2 (IGF-2) gene expression is an independent predictor of poor survival for patients with advanced stage serous epithelial ovarian cancer. Gynecol Oncol 2005; 96 (2): 355-61.
  53. Soufla G, Sifakis S, Spandidos D.A. FGF2 transcript levels are positively correlated with EGF and IGF-1 in the malignant endometrium. Cancer letters 2008; 259 (2): 146-55.
  54. Spentzos D et al. IGF axis gene expression patterns are prognostic of survival in epithelial ovarian cancer. Endocrine - related Cancer 2007; 14 (3): 781-90.
  55. Steuerman R, Shevah O, Laron Z. Congenital IGF1 deficiency tends to confer protection against post - natal development of malignancies. Eur J Endocrinol 2011; 164 (4): 485-9.
  56. Tas F et al. Clinical significance of serum insulin - like growth factor-1 (IGF-1) and insulinlike growth factor binding protein-3 (IGFBP-3) in patients with epithelial ovarian cancer. Tumor Biol 2014; 35 (4): 3125-32.
  57. Wagner A.D et al. Vascular - endothelial - growth - factor (VEGF) targeting therapies for endocrine refractory or resistant metastatic breast cancer. Cochrane Database Syst Rev 2012; 7.
  58. Wang F et al. Vascular endothelial growth factor - regulated ovarian cancer invasion and migration involves expression and activation of matrix metalloproteinases. Int J Cancer 2006; 118 (4): 879-88.
  59. Wang H et al. The expression of VEGF and Dll4/Notch pathway molecules in ovarian cancer. Clinica Chimica Acta 2014; 436: 243-48.
  60. Werner H, Bruchim I. IGF-1 and BRCA1 signalling pathways in familial cancer. Lancet Oncol 2012; 13 (12): e537-e544.
  61. Wong C, Wellman T.L, Lounsbury K.M. VEGF and HIF-1a expression are increased in advanced stages of epithelial ovarian cancer. Gynecol Oncol 2003; 91 (3): 513-7.

© ООО "Консилиум Медикум", 2015

Creative Commons License
Эта статья доступна по лицензии Creative Commons Attribution-NonCommercial 4.0 International License.
 


Данный сайт использует cookie-файлы

Продолжая использовать наш сайт, вы даете согласие на обработку файлов cookie, которые обеспечивают правильную работу сайта.

О куки-файлах