UDC: 615.277.3+616-006.04
BBC: Р281.82+Р56,4-3
Shamitova E.N., Matkov K.G., Shikhranova D.D., Abdullin R.R.
Neutralization of Angiopoietin-2 and Vascular Endothelial Growth Factor (VEGF) for Therapeutic Purposes
Keywords: angiopoietin-2, angiogenesis, angiogenesis factors, tumor angiogenesis, angiogenesis inhibitors, VEGF, vascular endothelial growth factor
New blood vessels in organs and tissues are formed by angiogenesis, which can take place both in the normal condition and in tumour growth. Angiogenesis supports the strength and integrity of the connections in blood vessel endothelial cells with each other and with the basement membrane. This ensures nutrition of tissues and organs, saturation with oxygen, macronutrients and micronutrients. Along with this, angiogenesis contributes to timely elimination of metabolic products. Metastatic spreading and tumor growth are supported by uncontrolled angiogenesis, that is why it is important to study the works dedicated to neutralization of angiogenesis factors, which becomes a method of combating various oncological diseases and other pathologies. The aim of this work was to study the information about modern drugs, including those at the stage of clinical trials, capable of neutralizing angiopoietin-2 – an inhibitor of angiogenesis and vascular growth factor (VEGF) – an angiogenesis activator, to evaluate the effectiveness and safety of various doses of drugs in various pathologies, to analyze the current state of studying tumor angiogenesis, achievements and prospects for the use of antiangiogenic drugs in oncological practice. The main focus was on the role of angiogenesis inhibitors and activators. To construct and structure the meta-analysis, we conducted a systematic review of the literature, searching works in open Internet resources such as PubMed, CyberLeninka, PsycINFO, Elibrary, published in the period from January 1, 2016 to March 31, 2021, devoted to studies on the effectiveness of drugs aimed at neutralizing angiopoietin-2 and VEGF. Conference materials and dissertations were analyzed to obtain additional data on research in this area.
References
- Gosudarstvennyi Reestr Lekarstvennykh Sredstv [State Register of Medicines], LSR-004567/08. Available at: https://grls.rosminzdrav.ru/Default.aspx.
- Cheberda A.E., Belousov D.Yu., Shishkin M.M. Farmakoekonomicheskii analiz primeneniya ranibizumaba i aflibertsepta dlya lecheniya patsientov s diabeticheskim makulyarnym otekom [Pharmacoeconomic analysis of ranibizumab and afl ibercept for treatment of diabetic macular edema]. Kachestvennaya klinicheskaya praktika, 2017, no.4, pp. 17–30.
- Chekhonin V.P., Shein S.A., Korchagina A.A., Gurina O.I. Rol’ vegf v razvitii neoplasticheskogo angiogeneza [VEGF in neoplastic angiogenesis]. Vestnik RAMN, 2012, no. 2, pp. 23–34.
- Yarmonenko C. P. Novaya paradigma kombinirovannoi antiangiogenno-tsitotoksicheskoi terapii raka [A new paradigm for combination antiangiogeic-cytotoxic tumor therapy]. Rossiiskii bioterapevticheskii zhurnal, 2005, no. 4, pp. 50–58.
- Bach F., Uddin F.J., Burke D. Angiopoietins in malignancy. Eur J Surg Oncol, 2007, vol. 33, no. 1, pp. 7–15.
- Bertolini F., Shaked Y., Mancuso P., Kerbel R.S. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer, 2006, vol. 6, no. 11, pp. 835–845.
- Birbrair A., Zhang T., Wang Z.M., Messi M.L., Olson J.D., Mintz A., Delbono O. Type-2 pericytes participate in normal and tumoral angiogenesis. Am J Physiol Cell Physiol, 2014, vol. 307, no. 1, pp. 25–38.
- Brauer P.R. Role in cardeiovascular development and disease. Fronot Biosci, 2006, vol. 11, pp. 447–478.
- Carmeliet P., Jain R.K. Molecular mechanisms and clinical applications of angiogenesis. Nature, 2011, vol. 473, no. 7347, pp. 298–307.
- Ciombor K. K., Berlin J., Chano E. Aflibercept. Clinical cancer research: an official journal of the American Association for Cancer Research, 2013, vol. 19, no. 8, pp. 1920–1925.
- Colleoni M., Rocca A., Sandri M.T., Zorzino L., Masci G. et al. Low-dose oral methotrexate and cyclophosphamide in metastatic breast cancer: antitumor activity and correlation with vascular endothelial growth factor levels. Ann Oncol, 2002, vol. 13, no. 1, pp. 73–80.
- Ferrara N. Vascular endothelial growth factor: basic science and clinical progress. Rev, 2004, vol. 25, no. 4, pp. 581–611.
- Folkman J. Tumor angiogenesis: therapeutic implications. N Engl J Med, 1971, vol. 285, no. 21, pp. 1182–1186.
- Ghiringhelli F., Menard C., Puig P.E., Ladoire S., Roux S. et al. Metronomic cyclophosphamide regimen selectively depletes CD4+CD25+ regulatory T cells and restores T and NK effector functions in end stage cancer patients. Cancer Immunol Immunother, 2007, vol. 56, no. 5, pp. 641–648.
- Hu B., Cheng S.Y. Angiopoietin-2: development of inhibitors for cancer therapy. Curr Oncol Rep, 2009, vol. 11, no. 2, pp. 111–116.
- Hu X., Cao J., Hu W., Wu C., Pan Y. et al. Multicenter phase II study of apatinib in non-triple-negative metastatic breast cancer. BMC Cancer, 2014, vol. 14, p. 820.
- Hurwitz H., Saini S. Bevacizumab in the Treatment of Metastatic Colorectal Cancer: Safety Profile and Management of Adverse Events. Seminars in oncology, 2006, vol. 33, pp. 26–34.
- Kamphaus G.D., Colorado P.C., Panka D.J., Hopfer H., Ramchandran R. et al. Canstatin, a novel matrix-derived inhibitor of angiogenesis and tumor growth. J Biol Chem, 2000, vol. 275, no. 2, pp. 1209–1215.
- Kertes P.J., Galic I.J., Greve M., Williams G., Baker J., Lahaie M., Sheidow T. Efficacy of a Treat-and-Extend Regimen With Ranibizumab in Patients With Neovascular Age-Related Macular Disease: A Randomized Clinical Trial. JAMA Ophthalmol., 2020, vol. 138, no. 3, pp. 244–250.
- Khanani A.M., Patel S.S., Ferrone P.J., Osborne A., Sahni J. et al. Efficacy of Every Four Monthly and Quarterly Dosing of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The STAIRWAY Phase 2 Randomized Clinical Trial. JAMA Ophthalmol, 2020, vol. 138, no. 9, pp. 964–972.
- Kristensen T., Knutsson M., Wehland M., Laursen B., Grimm D., Warnke E., Magnusson N. Anti-Vascular Endothelial Growth Factor Therapy in Breast Cancer. International journal of molecular sciences, 2014, vol. 15, no. 12, pp. 23024–23041.
- Lee M.Y., Kim S.H., Kim H.S. et al. Inhibition of hypoxia-induced angiogenesis by FK228, a specific histone deacetylase inhibitor, via suppression of HIF-1α Biochemical and Biophysical Research Communications, 2003, vol. 300, no. 1, pp. 241–246.
- Lu X., Sun X. Profile of conbercept in the treatment of neovascular age-related macular degeneration. Drugh Design, Development and Thersapy, 2015, no. 9, pp. 2311–2320.
- Martin-Padura I., Marighetti P., Agliano A., Colombo F., Larzabal L. et al. Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts. Lab Invest, 2012, vol. 92, no. 7, pp. 952–966.
- Niu G., Chen X. Vascular endothelial growth factor as an anti-angiogenic target for cancer therapy. Curr Drug Targets, 2010, vol. 11, no. 8, pp. 1000–1017.
- O’Reilly M.S., Boehm T., Shing Y., Fukai N., Vasios G. et al. Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell, 1997, vol. 88, no. 2, pp. 277–285.
- Pike S.E., Yao L., Setsuda J., Jones K.D., Cherney B. et al. Calreticulin and calreticulin fragments are endothelial cell inhibitors that suppress tumor growth. Blood, 1999, vol. 94, no. 7, pp. 2461–2468.
- Sahni J., Dugel P.U., Patel S.S., Chittum M.E., Berger B. et al. Safety and Efficacy of Different Doses and Regimens of Faricimab vs Ranibizumab in Neovascular Age-Related Macular Degeneration: The AVENUE Phase 2 Randomized Clinical Trial. JAMA Ophthalmol, 2020, vol. 138, no. 9, pp. 955–963.
- Sahni J., Patel S.S., Dugel P.U., Khanani A.M., Jhaveri C.D. et al. Simultaneous Inhibition of Angiopoietin-2 and Vascular Endothelial Growth Factor-A with Faricimab in Diabetic Macular Edema: BOULEVARD Phase 2 Randomized Trial. Ophthalmology, 2019, vol. 126, no. 8, pp. 1155–1170.
- Wedam S.B., Low J.A., Yang S.X., Chow C.K., Choyke P. et al. Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol, 2006, vol. 24, no. 5, pp. 769–777.
- Wong W.L., Su X., Li X., Cheung C.M., Klein R., Cheng C.Y., Wong T.Y. Global prevalence of age-related macular degeneration and disease burden projection for 2020 and 2040: a systematic review and meta-analysis. Lancet Glob Health, 2014, vol. 2, no. 2, pp. 106–116.
- Zhang Y., Han Q., Ru Y., Bo Q., Wei R. Anti-VEGF treatment for myopic choroid neovascularization: From molecular characterization to update on clinical application. Drug design, development and therapy, 2015, no. 9, pp. 3413–3421.
About authors
- Shamitova Elena N.
- Candidate of Biological Sciences, Associate Professor, Department of Pharmacology, Clinical Pharmacology and Biochemistry, Chuvash State University, Russia, Cheboksary (shamitva@mail.ru; ORCID: https://orcid.org/0000-0002-4642-7822)
- Matkov Konstantin G.
- Candidate of Biological Sciences, Associate Professor, Department of Pharmacology, Clinical Pharmacology and Biochemistry, Chuvash State University, Russia, Cheboksary (shamitva@mail.ru; )
- Shikhranova Darya D.
- Student of the Medicine Faculty, Chuvash State University, Russia, Cheboksary (dashulyash@mail.ru; )
- Abdullin Ramis R.
- Student of the Medicine Faculty, Chuvash State University, Russia, Cheboksary (aramis.tat-1998@mail.ru; )
Article link
Shamitova E.N., Matkov K.G., Shikhranova D.D., Abdullin R.R. Neutralization of Angiopoietin-2 and Vascular Endothelial Growth Factor (VEGF) for Therapeutic Purposes [Electronic resource] // Acta medica Eurasica. – 2021. – №2. P. 64-79. – URL: https://acta-medica-eurasica.ru/en/single/2021/2/8/. DOI: 10.47026/2413-4864-2021-2-64-79.