{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T17:31:00Z","timestamp":1793035860802,"version":"4.5.0"},"reference-count":222,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,1,4]],"date-time":"2024-01-04T00:00:00Z","timestamp":1704326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Pharmacol."],"abstract":"<jats:p>Vascular endothelial growth factors (VEGF), Vascular endothelial growth factor receptors (VEGFR) and their downstream signaling pathways are promising targets in anti-angiogenic therapy. They constitute a crucial system to regulate physiological and pathological angiogenesis. In the last 20\u00a0years, many anti-angiogenic drugs have been developed based on VEGF\/VEGFR system to treat diverse cancers and retinopathies, and new drugs with improved properties continue to emerge at a fast rate. They consist of different molecular structures and characteristics, which enable them to inhibit the interaction of VEGF\/VEGFR, to inhibit the activity of VEGFR tyrosine kinase (TK), or to inhibit VEGFR downstream signaling. In this paper, we reviewed the development of marketed anti-angiogenic drugs involved in the VEGF\/VEGFR axis, as well as some important drug candidates in clinical trials. We discuss their mode of action, their clinical benefits, and the current challenges that will need to be addressed by the next-generation of anti-angiogenic drugs. We focus on the molecular structures and characteristics of each drug, including those approved only in China.<\/jats:p>","DOI":"10.3389\/fphar.2023.1307860","type":"journal-article","created":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T23:24:13Z","timestamp":1704324253000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":152,"title":["Recent advances of anti-angiogenic inhibitors targeting VEGF\/VEGFR axis"],"prefix":"10.3389","volume":"14","author":[{"given":"Lei","family":"Wang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wang-Qing","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sylvain","family":"Broussy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bingnan","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongming","family":"Fang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,1,4]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1016","DOI":"10.1007\/s10637-018-0591-z","article-title":"A phase I, open-label, two-stage study to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of the oral AKT inhibitor GSK2141795 in patients with solid tumors","volume":"36","author":"Aghajanian","year":"2018","journal-title":"Invest. New Drugs"},{"key":"B2","doi-asserted-by":"publisher","first-page":"197","DOI":"10.1002\/(SICI)1097-0282(1998)47:3<197::AID-BIP2>3.0.CO;2-H","article-title":"Protein tyrosine kinases: structure, substrate specificity, and drug discovery","volume":"47","author":"Al-Obeidi","year":"1998","journal-title":"Biopolymers"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1771","DOI":"10.1007\/s40265-016-0661-5","article-title":"Cabozantinib: a review in advanced renal cell carcinoma","volume":"76","author":"Al-Salama","year":"2016","journal-title":"Drugs"},{"key":"B4","doi-asserted-by":"publisher","first-page":"665","DOI":"10.1007\/s40265-019-01116-x","article-title":"Lenvatinib: a review in hepatocellular carcinoma","volume":"79","author":"Al-Salama","year":"2019","journal-title":"Drugs"},{"key":"B5","doi-asserted-by":"publisher","first-page":"S45","DOI":"10.3747\/co.25.3747","article-title":"Antiangiogenic therapies in non-small-cell lung cancer","volume":"25","author":"Alshangiti","year":"2018","journal-title":"Curr. Oncol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"125","DOI":"10.1016\/j.semcancer.2019.07.009","article-title":"PI3K\/Akt\/mTOR inhibitors in cancer: at the bench and bedside","volume":"59","author":"Alzahrani","year":"2019","journal-title":"Semin. Cancer Biol."},{"key":"B7","doi-asserted-by":"publisher","first-page":"413","DOI":"10.1007\/s40123-021-00354-1","article-title":"A review of aflibercept treatment for macular disease","volume":"10","author":"Anguita","year":"2021","journal-title":"Ophthalmol. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1016\/j.cell.2019.01.021","article-title":"VEGF in signaling and disease: beyond discovery and development","volume":"176","author":"Apte","year":"2019","journal-title":"Cell"},{"key":"B9","doi-asserted-by":"publisher","first-page":"102247","DOI":"10.1016\/j.jbc.2022.102247","article-title":"Structural features of the protein kinase domain and targeted binding by small-molecule inhibitors","volume":"298","author":"Arter","year":"2022","journal-title":"J. Biol. Chem."},{"key":"B10","doi-asserted-by":"publisher","first-page":"58","DOI":"10.5301\/ejo.5001060","article-title":"Pegaptanib: choroidal neovascularization in patients with age-related macular degeneration and previous arterial thromboembolic events","volume":"28","author":"Battaglia Parodi","year":"2018","journal-title":"Eur. J. Ophthalmol."},{"key":"B11","doi-asserted-by":"publisher","first-page":"2021","DOI":"10.2217\/fon-2017-0689","article-title":"Lenvatinib and its use in the treatment of unresectable hepatocellular carcinoma","volume":"14","author":"Baxter","year":"2018","journal-title":"Future Oncol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"2801","DOI":"10.2147\/DDDT.S109640","article-title":"Axitinib in the treatment of renal cell carcinoma: design, development, and place in therapy","volume":"11","author":"Bellesoeur","year":"2017","journal-title":"Drug Des. Devel Ther."},{"key":"B13","doi-asserted-by":"publisher","first-page":"868","DOI":"10.1038\/nrd3531","article-title":"Rapamycin passes the torch: a new generation of mTOR inhibitors","volume":"10","author":"Benjamin","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"B14","doi-asserted-by":"publisher","first-page":"1847","DOI":"10.1007\/s40265-018-1013-4","article-title":"Duvelisib: first global approval","volume":"78","author":"Blair","year":"2018","journal-title":"Drugs"},{"key":"B15","doi-asserted-by":"publisher","first-page":"1108","DOI":"10.1634\/theoncologist.2012-0044","article-title":"FDA approval summary: sunitinib for the treatment of progressive well-differentiated locally advanced or metastatic pancreatic neuroendocrine tumors","volume":"17","author":"Blumenthal","year":"2012","journal-title":"Oncologist"},{"key":"B16","doi-asserted-by":"publisher","first-page":"1473","DOI":"10.1158\/1538-7445.AM2021-1473","article-title":"Abstract 1473: nonclinical development of PF-07284890 (ARRY-461), a potent, brain-penetrant, small molecule inhibitor of BRAF V600-mutation-driven tumors in vitro and in vivo","volume":"81","author":"Bouhana","year":"2021","journal-title":"Cancer Res."},{"key":"B17","doi-asserted-by":"publisher","first-page":"1781","DOI":"10.1182\/blood-2011-11-390922","article-title":"Thermodynamic and structural description of allosterically regulated VEGFR-2 dimerization","volume":"119","author":"Brozzo","year":"2012","journal-title":"Blood"},{"key":"B18","doi-asserted-by":"publisher","first-page":"e388","DOI":"10.1016\/S1470-2045(18)30503-5","article-title":"Fruquintinib for previously treated metastatic colorectal cancer","volume":"19","author":"Burki","year":"2018","journal-title":"Lancet Oncol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1016\/j.ctrv.2015.11.003","article-title":"Lenvatinib: role in thyroid cancer and other solid tumors","volume":"42","author":"Cabanillas","year":"2016","journal-title":"Cancer Treat. Rev."},{"key":"B20","doi-asserted-by":"publisher","first-page":"3471","DOI":"10.2147\/DDDT.S177192","article-title":"The efficacy and safety of aflibercept and conbercept in diabetic macular edema","volume":"12","author":"Cai","year":"2018","journal-title":"Drug Des. Devel Ther."},{"key":"B21","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1358\/dot.2007.43.8.1120868","article-title":"Targeted pharmacotherapy of retinal diseases with ranibizumab","volume":"43","author":"Campochiaro","year":"2007","journal-title":"Drugs Today (Barc)."},{"key":"B22","doi-asserted-by":"publisher","first-page":"476","DOI":"10.1038\/s41573-023-00671-z","article-title":"Targeting angiogenesis in oncology, ophthalmology and beyond","volume":"22","author":"Cao","year":"2023","journal-title":"Nat. Rev. Drug Discov."},{"key":"B23","doi-asserted-by":"publisher","first-page":"653","DOI":"10.1038\/nm0603-653","article-title":"Angiogenesis in health and disease","volume":"9","author":"Carmeliet","year":"2003","journal-title":"Nat. Med."},{"key":"B24","doi-asserted-by":"publisher","first-page":"1232","DOI":"10.1200\/Jco.2017.74.1090","article-title":"Selumetinib in combination with dacarbazine in patients with metastatic uveal melanoma: a phase III, multicenter, randomized trial (sumit)","volume":"36","author":"Carvajal","year":"2018","journal-title":"J. Clin. Oncol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1186\/s12885-016-2463-2","article-title":"Efficacy of sorafenib in BRAF-mutated non-small-cell lung cancer (NSCLC) and no response in synchronous BRAF wild type-hepatocellular carcinoma: a case report","volume":"16","author":"Casadei Gardini","year":"2016","journal-title":"BMC Cancer"},{"key":"B26","doi-asserted-by":"publisher","first-page":"1388","DOI":"10.3390\/ijms21041388","article-title":"Role of VEGFs\/VEGFR-1 signaling and its inhibition in modulating tumor invasion: experimental evidence in different metastatic cancer models","volume":"21","author":"Ceci","year":"2020","journal-title":"Int. J. Mol. Sci."},{"key":"B27","doi-asserted-by":"publisher","first-page":"1258","DOI":"10.1016\/S0140-6736(13)61501-9","article-title":"Alternative treatments to inhibit VEGF in age-related choroidal neovascularisation: 2-year findings of the IVAN randomised controlled trial","volume":"382","author":"Chakravarthy","year":"2013","journal-title":"Lancet"},{"key":"B28","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1146\/annurev.pathol.4.110807.092311","article-title":"PTEN and the PI3-kinase pathway in cancer","volume":"4","author":"Chalhoub","year":"2009","journal-title":"Annu. Rev. Pathol."},{"key":"B29","doi-asserted-by":"publisher","first-page":"991","DOI":"10.1080\/14712598.2021.1928629","article-title":"Ranibizumab for the treatment of diabetic retinopathy","volume":"21","author":"Chatziralli","year":"2021","journal-title":"Expert Opin. Biol. Ther."},{"key":"B30","doi-asserted-by":"publisher","first-page":"865","DOI":"10.1006\/jmbi.1999.3192","article-title":"Selection and analysis of an optimized anti-VEGF antibody: crystal structure of an affinity-matured Fab in complex with antigen","volume":"293","author":"Chen","year":"1999","journal-title":"J. Mol. Biol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1636","DOI":"10.1158\/1535-7163.MCT-13-0753","article-title":"Differential antitumor activity of aflibercept and bevacizumab in patient-derived xenograft models of colorectal cancer","volume":"13","author":"Chiron","year":"2014","journal-title":"Mol. Cancer Ther."},{"key":"B32","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1007\/s10555-014-9538-9","article-title":"Anti-vascular therapies in ovarian cancer: moving beyond anti-VEGF approaches","volume":"34","author":"Choi","year":"2015","journal-title":"Cancer Metastasis Rev."},{"key":"B33","doi-asserted-by":"publisher","first-page":"505","DOI":"10.1038\/nrc2868","article-title":"Targeting the tumour vasculature: insights from physiological angiogenesis","volume":"10","author":"Chung","year":"2010","journal-title":"Nat. Rev. Cancer"},{"key":"B34","doi-asserted-by":"publisher","first-page":"1887","DOI":"10.2146\/ajhp130143","article-title":"Ziv-aflibercept: a novel angiogenesis inhibitor for the treatment of metastatic colorectal cancer","volume":"70","author":"Chung","year":"2013","journal-title":"Am. J. Health Syst. Pharm."},{"key":"B35","doi-asserted-by":"publisher","first-page":"856316","DOI":"10.3389\/fgwh.2022.856316","article-title":"Endometriosis-associated angiogenesis and anti-angiogenic therapy for endometriosis","volume":"3","author":"Chung","year":"2022","journal-title":"Front. Glob. Womens Health"},{"key":"B36","doi-asserted-by":"publisher","first-page":"1920","DOI":"10.1158\/1078-0432.CCR-12-2911","article-title":"Aflibercept","volume":"19","author":"Ciombor","year":"2013","journal-title":"Clin. Cancer Res."},{"key":"B37","doi-asserted-by":"publisher","first-page":"309","DOI":"10.1038\/nrd773","article-title":"Protein kinases--the major drug targets of the twenty-first century?","volume":"1","author":"Cohen","year":"2002","journal-title":"Nat. Rev. Drug Discov."},{"key":"B38","doi-asserted-by":"publisher","first-page":"1521","DOI":"10.1016\/j.ejca.2013.01.013","article-title":"A phase I dose-finding, safety and tolerability study of AZD8330 in patients with advanced malignancies","volume":"49","author":"Cohen","year":"2013","journal-title":"Eur. J. Cancer"},{"key":"B39","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1016\/j.ygyno.2015.04.005","article-title":"A phase II evaluation of selumetinib (AZD6244, ARRY-142886), a selective MEK-1\/2 inhibitor in the treatment of recurrent or persistent endometrial cancer: an NRG Oncology\/Gynecologic Oncology Group study","volume":"138","author":"Coleman","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"B40","doi-asserted-by":"publisher","first-page":"e656","DOI":"10.1097\/HS9.0000000000000656","article-title":"A phase II study to assess the safety and efficacy of the dual mTORC1\/2 and PI3K inhibitor bimiralisib (PQR309) in relapsed, refractory lymphoma","volume":"5","author":"Collins","year":"2021","journal-title":"Hemasphere"},{"key":"B41","doi-asserted-by":"publisher","first-page":"1685","DOI":"10.1177\/1060028013509792","article-title":"Regorafenib: a novel multitargeted tyrosine kinase inhibitor for colorectal cancer and gastrointestinal stromal tumors","volume":"47","author":"Crona","year":"2013","journal-title":"Ann. Pharmacother."},{"key":"B42","doi-asserted-by":"publisher","first-page":"3375","DOI":"10.3390\/ijms23063375","article-title":"Relationship between VEGF family members, their receptors and cell death in the neoplastic transformation of colorectal cancer","volume":"23","author":"Dakowicz","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B43","doi-asserted-by":"publisher","first-page":"198","DOI":"10.3390\/cells9010198","article-title":"Targeting aberrant RAS\/RAF\/MEK\/ERK signaling for cancer therapy","volume":"9","author":"Degirmenci","year":"2020","journal-title":"Cells"},{"key":"B44","doi-asserted-by":"publisher","first-page":"e062036","DOI":"10.1136\/bmjopen-2022-062036","article-title":"Erlotinib plus bevacizumab versus erlotinib alone in patients with EGFR-positive advanced non-small-cell lung cancer: a systematic review and meta-analysis of randomised controlled trials","volume":"12","author":"Deng","year":"2022","journal-title":"BMJ Open"},{"key":"B45","doi-asserted-by":"publisher","first-page":"3","DOI":"10.1186\/s40942-016-0026-y","article-title":"Fusion proteins for treatment of retinal diseases: aflibercept, ziv-aflibercept, and conbercept","volume":"2","author":"De Oliveira Dias","year":"2016","journal-title":"Int. J. Retina Vitr."},{"key":"B46","doi-asserted-by":"publisher","first-page":"457","DOI":"10.1038\/nrc.2017.51","article-title":"Microenvironmental regulation of tumour angiogenesis","volume":"17","author":"De Palma","year":"2017","journal-title":"Nat. Rev. Cancer"},{"key":"B47","doi-asserted-by":"publisher","first-page":"1270","DOI":"10.1007\/s12325-017-0548-1","article-title":"Ranibizumab in the treatment of diabetic macular edema: a review of the current status, unmet needs, and emerging challenges","volume":"34","author":"Dervenis","year":"2017","journal-title":"Adv. Ther."},{"key":"B48","doi-asserted-by":"publisher","first-page":"1823","DOI":"10.1038\/sj.bjc.6603176","article-title":"Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature","volume":"94","author":"Des Guetz","year":"2006","journal-title":"Br. J. Cancer"},{"key":"B49","doi-asserted-by":"publisher","first-page":"349","DOI":"10.1007\/s10637-014-0191-5","article-title":"Phase I study of XL281 (BMS-908662), a potent oral RAF kinase inhibitor, in patients with advanced solid tumors","volume":"33","author":"Dickson","year":"2015","journal-title":"Invest. New Drugs"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1421","DOI":"10.1517\/14656566.6.8.1421","article-title":"Pegaptanib: the first antiangiogenic agent approved for neovascular macular degeneration","volume":"6","author":"Doggrell","year":"2005","journal-title":"Expert Opin. Pharmacother."},{"key":"B51","doi-asserted-by":"publisher","first-page":"e0233116","DOI":"10.1371\/journal.pone.0233116","article-title":"DLX1008 (brolucizumab), a single-chain anti-VEGF-A antibody fragment with low picomolar affinity, leads to tumor involution in an in vivo model of Kaposi Sarcoma","volume":"15","author":"Eason","year":"2020","journal-title":"PLoS One"},{"key":"B52","doi-asserted-by":"publisher","first-page":"102221","DOI":"10.1016\/j.ctrv.2021.102221","article-title":"Cabozantinib: an evolving therapy for hepatocellular carcinoma","volume":"98","author":"El-Khoueiry","year":"2021","journal-title":"Cancer Treat. Rev."},{"key":"B53","doi-asserted-by":"publisher","first-page":"1629","DOI":"10.3390\/biom12111629","article-title":"Current and novel therapeutic approaches for treatment of neovascular age-related macular degeneration","volume":"12","author":"Elsheikh","year":"2022","journal-title":"Biomolecules"},{"key":"B123","doi-asserted-by":"publisher","first-page":"48","DOI":"10.1177\/1758834015616934","article-title":"Combination therapy with BRAF and MEK inhibitors for melanoma: latest evidence and place in therapy","volume":"8","author":"Eroglu","year":"2016","journal-title":"Ther. Adv. Med. Oncol."},{"key":"B54","doi-asserted-by":"publisher","first-page":"177","DOI":"10.1080\/14737140.2019.1559058","article-title":"Sorafenib: key lessons from over 10 years of experience","volume":"19","author":"Escudier","year":"2019","journal-title":"Expert Rev. Anticancer Ther."},{"key":"B55","doi-asserted-by":"publisher","first-page":"10","DOI":"10.1167\/tvst.5.2.10","article-title":"VEGF and intraocular neovascularization: from discovery to therapy","volume":"5","author":"Ferrara","year":"2016","journal-title":"Transl. Vis. Sci. Technol."},{"key":"B56","doi-asserted-by":"publisher","first-page":"385","DOI":"10.1038\/nrd.2015.17","article-title":"Ten years of anti-vascular endothelial growth factor therapy","volume":"15","author":"Ferrara","year":"2016","journal-title":"Nat. Rev. Drug Discov."},{"key":"B57","doi-asserted-by":"publisher","first-page":"859","DOI":"10.1097\/01.iae.0000242842.14624.e7","article-title":"Development of ranibizumab, an anti-vascular endothelial growth factor antigen binding fragment, as therapy for neovascular age-related macular degeneration","volume":"26","author":"Ferrara","year":"2006","journal-title":"Retina"},{"key":"B58","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1210\/edrv.18.1.0287","article-title":"The biology of vascular endothelial growth factor","volume":"18","author":"Ferrara","year":"1997","journal-title":"Endocr. Rev."},{"key":"B59","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nm0603-669","article-title":"The biology of VEGF and its receptors","volume":"9","author":"Ferrara","year":"2003","journal-title":"Nat. Med."},{"key":"B60","doi-asserted-by":"publisher","first-page":"967","DOI":"10.1038\/nature04483","article-title":"Angiogenesis as a therapeutic target","volume":"438","author":"Ferrara","year":"2005","journal-title":"Nature"},{"key":"B61","doi-asserted-by":"publisher","first-page":"735","DOI":"10.1080\/14712598.2019.1627322","article-title":"Clinical efficacy and safety of ranibizumab in the treatment of wet age-related macular degeneration","volume":"19","author":"Ferro Desideri","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"B62","doi-asserted-by":"publisher","first-page":"942","DOI":"10.1038\/nrc2524","article-title":"FLT1 and its ligands VEGFB and PlGF: drug targets for anti-angiogenic therapy?","volume":"8","author":"Fischer","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"B63","doi-asserted-by":"publisher","first-page":"1032","DOI":"10.1002\/cncr.23678","article-title":"Hypoxia-regulated protein expression, patient characteristics, and preoperative imaging as predictors of survival in adults with glioblastoma multiforme","volume":"113","author":"Flynn","year":"2008","journal-title":"Cancer"},{"key":"B64","first-page":"5407","article-title":"High tumor levels of vascular endothelial growth factor predict poor response to systemic therapy in advanced breast cancer","volume":"61","author":"Foekens","year":"2001","journal-title":"Cancer Res."},{"key":"B65","doi-asserted-by":"publisher","first-page":"1182","DOI":"10.1056\/NEJM197111182852108","article-title":"Tumor angiogenesis: therapeutic implications","volume":"285","author":"Folkman","year":"1971","journal-title":"N. Engl. J. Med."},{"key":"B66","doi-asserted-by":"publisher","first-page":"409","DOI":"10.1097\/00000658-197203000-00014","article-title":"Anti-angiogenesis: new concept for therapy of solid tumors","volume":"175","author":"Folkman","year":"1972","journal-title":"Ann. Surg."},{"key":"B67","doi-asserted-by":"publisher","first-page":"96","DOI":"10.7326\/0003-4819-82-1-96","article-title":"Tumor angiogenesis: a possible control point in tumor growth","volume":"82","author":"Folkman","year":"1975","journal-title":"Ann. Intern Med."},{"key":"B68","doi-asserted-by":"publisher","first-page":"1097","DOI":"10.1016\/j.str.2011.01.019","article-title":"The structural basis for the function of two anti-VEGF receptor 2 antibodies","volume":"19","author":"Franklin","year":"2011","journal-title":"Structure"},{"key":"B69","doi-asserted-by":"publisher","first-page":"3741","DOI":"10.1016\/j.bmcl.2013.05.007","article-title":"Discovery of NVP-BYL719 a potent and selective phosphatidylinositol-3 kinase alpha inhibitor selected for clinical evaluation","volume":"23","author":"Furet","year":"2013","journal-title":"Bioorg Med. Chem. Lett."},{"key":"B70","doi-asserted-by":"publisher","first-page":"1001","DOI":"10.3892\/ol.2020.11685","article-title":"Anlotinib as a molecular targeted therapy for tumors","volume":"20","author":"Gao","year":"2020","journal-title":"Oncol. Lett."},{"key":"B71","doi-asserted-by":"publisher","first-page":"102017","DOI":"10.1016\/j.ctrv.2020.102017","article-title":"Bevacizumab (Avastin\u00ae) in cancer treatment: a review of 15\u00a0years of clinical experience and future outlook","volume":"86","author":"Garcia","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"B72","doi-asserted-by":"publisher","first-page":"175586","DOI":"10.1016\/j.ejphar.2023.175586","article-title":"The role of VEGF in cancer-induced angiogenesis and research progress of drugs targeting VEGF","volume":"949","author":"Ghalehbandi","year":"2023","journal-title":"Eur. J. Pharmacol."},{"key":"B73","doi-asserted-by":"publisher","first-page":"471","DOI":"10.1007\/s11523-021-00817-2","article-title":"Cardiovascular toxicities of antiangiogenic tyrosine kinase inhibitors: a retrospective, pharmacovigilance study","volume":"16","author":"Goldman","year":"2021","journal-title":"Target. Oncol."},{"key":"B74","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1586\/era.10.134","article-title":"Does axitinib (AG-01376) have a future role in metastatic renal cell carcinoma and other malignancies?","volume":"10","author":"Goldstein","year":"2010","journal-title":"Expert Rev. Anticancer Ther."},{"key":"B75","doi-asserted-by":"publisher","first-page":"1348","DOI":"10.1016\/j.yexcr.2013.02.021","article-title":"Regulation of angiogenesis by PI3K signaling networks","volume":"319","author":"Graupera","year":"2013","journal-title":"Exp. Cell Res."},{"key":"B76","doi-asserted-by":"publisher","first-page":"269","DOI":"10.4137\/CMO.S10594","article-title":"Axitinib: a review of its safety and efficacy in the treatment of adults with advanced renal cell carcinoma","volume":"7","author":"Gross-Goupil","year":"2013","journal-title":"Clin. Med. Insights Oncol."},{"key":"B77","doi-asserted-by":"publisher","first-page":"101993","DOI":"10.1016\/j.ctrv.2020.101993","article-title":"Evolving role of regorafenib for the treatment of advanced cancers","volume":"86","author":"Grothey","year":"2020","journal-title":"Cancer Treat. Rev."},{"key":"B78","doi-asserted-by":"publisher","first-page":"515","DOI":"10.1007\/s10555-016-9637-x","article-title":"PI3K\/AKT\/mTOR: role in breast cancer progression, drug resistance, and treatment","volume":"35","author":"Guerrero-Zotano","year":"2016","journal-title":"Cancer Metastasis Rev."},{"key":"B79","doi-asserted-by":"publisher","first-page":"1569","DOI":"10.1001\/jamaoncol.2018.3039","article-title":"Effect of anlotinib as a third-line or further treatment on overall survival of patients with advanced non-small cell lung cancer: the ALTER 0303 phase 3 randomized clinical trial","volume":"4","author":"Han","year":"","journal-title":"JAMA Oncol."},{"key":"B80","doi-asserted-by":"publisher","first-page":"654","DOI":"10.1038\/bjc.2017.478","article-title":"Anlotinib as a third-line therapy in patients with refractory advanced non-small-cell lung cancer: a multicentre, randomised phase II trial (ALTER0302)","volume":"118","author":"Han","year":"","journal-title":"Br. J. Cancer"},{"key":"B81","doi-asserted-by":"publisher","first-page":"5495","DOI":"10.2147\/OTT.S112242","article-title":"Sunitinib: the antiangiogenic effects and beyond","volume":"9","author":"Hao","year":"2016","journal-title":"Onco Targets Ther."},{"key":"B82","doi-asserted-by":"publisher","first-page":"358","DOI":"10.1016\/S0140-6736(12)60868-X","article-title":"Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial","volume":"380","author":"Hauschild","year":"2012","journal-title":"Lancet"},{"key":"B83","doi-asserted-by":"publisher","first-page":"229","DOI":"10.1007\/s10238-021-00783-z","article-title":"Selumetinib: a selective MEK1 inhibitor for solid tumor treatment","volume":"23","author":"Hedayat","year":"2022","journal-title":"Clin. Exp. Med."},{"key":"B84","doi-asserted-by":"publisher","first-page":"729","DOI":"10.1016\/S0140-6736(22)00010-1","article-title":"Efficacy, durability, and safety of intravitreal faricimab up to every 16 weeks for neovascular age-related macular degeneration (TENAYA and LUCERNE): two randomised, double-masked, phase 3, non-inferiority trials","volume":"399","author":"Heier","year":"2022","journal-title":"Lancet"},{"key":"B85","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1097\/IAE.0000000000003003","article-title":"THE ANGIOPOIETIN\/TIE pathway in retinal vascular diseases: a review","volume":"41","author":"Heier","year":"2021","journal-title":"Retina"},{"key":"B86","doi-asserted-by":"publisher","first-page":"1414","DOI":"10.1161\/Circresaha.116.310477","article-title":"VEGFR3 modulates vascular permeability by controlling VEGF\/VEGFR2 signaling","volume":"120","author":"Heinolainen","year":"2017","journal-title":"Circulation Res."},{"key":"B87","doi-asserted-by":"publisher","first-page":"4774","DOI":"10.1158\/0008-5472.Can-07-6307","article-title":"BIBF 1120: triple angiokinase inhibitor with sustained receptor blockade and good antitumor efficacy","volume":"68","author":"Hilberg","year":"2008","journal-title":"Cancer Res."},{"key":"B88","doi-asserted-by":"publisher","first-page":"1870","DOI":"10.1200\/Jco.21.00714","article-title":"Selumetinib plus adjuvant radioactive iodine in patients with high-risk differentiated thyroid cancer: a phase III, randomized, placebo-controlled trial (astra)","volume":"40","author":"Ho","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"B89","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nature10912","article-title":"The translational landscape of mTOR signalling steers cancer initiation and metastasis","volume":"485","author":"Hsieh","year":"2012","journal-title":"Nature"},{"key":"B90","doi-asserted-by":"publisher","first-page":"16033","DOI":"10.1021\/acs.jmedchem.2c01070","article-title":"Targeting the PI3K\/AKT\/mTOR signaling pathway in the treatment of human diseases: current status, trends, and solutions","volume":"65","author":"Huang","year":"2022","journal-title":"J. Med. Chem."},{"key":"B91","doi-asserted-by":"publisher","first-page":"1385","DOI":"10.1158\/1078-0432.CCR-15-1354","article-title":"Safety and pharmacokinetics of lenvatinib in patients with advanced hepatocellular carcinoma","volume":"22","author":"Ikeda","year":"2016","journal-title":"Clin. Cancer Res."},{"key":"B92","doi-asserted-by":"publisher","first-page":"662","DOI":"10.1124\/dmd.111.043281","article-title":"Unique metabolic pathway of [(14)C]lenvatinib after oral administration to male cynomolgus monkey","volume":"40","author":"Inoue","year":"2012","journal-title":"Drug Metab. Dispos."},{"key":"B93","doi-asserted-by":"publisher","first-page":"23779","DOI":"10.1074\/jbc.M110.130658","article-title":"Structural insights into the binding of vascular endothelial growth factor-B by VEGFR-1(D2) recognition and specificity","volume":"285","author":"Iyer","year":"2010","journal-title":"J. Biol. Chem."},{"key":"B94","doi-asserted-by":"publisher","first-page":"2147","DOI":"10.2217\/fon-2020-0443","article-title":"Tivozanib, a highly potent and selective inhibitor of VEGF receptor tyrosine kinases, for the treatment of metastatic renal cell carcinoma","volume":"16","author":"Jacob","year":"2020","journal-title":"Future Oncol."},{"key":"B95","doi-asserted-by":"publisher","first-page":"751","DOI":"10.1007\/s00280-015-2842-4","article-title":"Absorption, distribution, metabolism, and excretion of [(14)C]BYL719 (alpelisib) in healthy male volunteers","volume":"76","author":"James","year":"2015","journal-title":"Cancer Chemother. Pharmacol."},{"key":"B96","doi-asserted-by":"publisher","first-page":"518","DOI":"10.1016\/S0140-6736(15)01088-0","article-title":"Antiangiogenic therapy in oncology: current status and future directions","volume":"388","author":"Jayson","year":"2016","journal-title":"Lancet"},{"key":"B97","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1016\/S0065-230X(09)02002-8","article-title":"PI3K\/PTEN signaling in angiogenesis and tumorigenesis","volume":"102","author":"Jiang","year":"2009","journal-title":"Adv. Cancer Res."},{"key":"B98","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1186\/s13046-020-01709-5","article-title":"The role of microenvironment in tumor angiogenesis","volume":"39","author":"Jiang","year":"2020","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"B99","doi-asserted-by":"publisher","first-page":"345","DOI":"10.1016\/S1470-2045(19)30817-4","article-title":"Fulvestrant plus capivasertib versus placebo after relapse or progression on an aromatase inhibitor in metastatic, oestrogen receptor-positive breast cancer (FAKTION): a multicentre, randomised, controlled, phase 2 trial","volume":"21","author":"Jones","year":"2020","journal-title":"Lancet Oncol."},{"key":"B100","doi-asserted-by":"publisher","first-page":"1305","DOI":"10.1038\/s41433-020-01377-x","article-title":"Angiopoietin\/Tie2 signalling and its role in retinal and choroidal vascular diseases: a review of preclinical data","volume":"35","author":"Joussen","year":"2021","journal-title":"Eye (Lond)."},{"key":"B101","doi-asserted-by":"publisher","first-page":"dev151019","DOI":"10.1242\/dev.151019","article-title":"Vascular endothelial growth factor signaling in development and disease","volume":"145","author":"Karaman","year":"2018","journal-title":"Development"},{"key":"B102","doi-asserted-by":"publisher","first-page":"e20210565","DOI":"10.1084\/jem.20210565","article-title":"Interplay of vascular endothelial growth factor receptors in organ-specific vessel maintenance","volume":"219","author":"Karaman","year":"2022","journal-title":"J. Exp. Med."},{"key":"B103","doi-asserted-by":"publisher","first-page":"74","DOI":"10.1038\/ni1013","article-title":"Vascular endothelial growth factor C is required for sprouting of the first lymphatic vessels from embryonic veins","volume":"5","author":"Karkkainen","year":"2004","journal-title":"Nat. Immunol."},{"key":"B104","doi-asserted-by":"publisher","first-page":"243","DOI":"10.1007\/s11523-017-0484-7","article-title":"Sorafenib: a review in hepatocellular carcinoma","volume":"12","author":"Keating","year":"2017","journal-title":"Target Oncol."},{"key":"B105","doi-asserted-by":"publisher","first-page":"633","DOI":"10.1358\/dot.2012.48.10.1860768","article-title":"Axitinib, a new therapeutic option in renal cell carcinoma","volume":"48","author":"Kessler","year":"2012","journal-title":"Drugs Today (Barc)."},{"key":"B106","doi-asserted-by":"publisher","first-page":"1135","DOI":"10.1080\/14712598.2019.1656715","article-title":"Ramucirumab for the treatment of gastric or gastro-esophageal junction cancer","volume":"19","author":"Khan","year":"2019","journal-title":"Expert Opin. Biol. Ther."},{"key":"B107","doi-asserted-by":"publisher","first-page":"1917","DOI":"10.1007\/s40265-017-0825-y","article-title":"Tivozanib: first global approval","volume":"77","author":"Kim","year":"2017","journal-title":"Drugs"},{"key":"B108","doi-asserted-by":"publisher","first-page":"120667","DOI":"10.1016\/j.saa.2021.120667","article-title":"The role of pro- and antiangiogenic factors in angiogenesis process by Raman spectroscopy","volume":"268","author":"Kopec","year":"2022","journal-title":"Spectrochim. Acta A Mol. Biomol. Spectrosc."},{"key":"B109","doi-asserted-by":"publisher","first-page":"36","DOI":"10.1016\/j.clinthera.2006.01.009","article-title":"Pegaptanib sodium for the treatment of neovascular age-related macular degeneration: a review","volume":"28","author":"Kourlas","year":"2006","journal-title":"Clin. Ther."},{"key":"B110","doi-asserted-by":"publisher","first-page":"2577","DOI":"10.2147\/DDDT.S142406","article-title":"Copanlisib for treatment of B-cell malignancies: the development of a PI3K inhibitor with considerable differences to idelalisib","volume":"12","author":"Krause","year":"2018","journal-title":"Drug Des. Devel Ther."},{"key":"B111","doi-asserted-by":"publisher","first-page":"32521","DOI":"10.1074\/jbc.272.51.32521","article-title":"The vascular endothelial growth factor receptor KDR activates multiple signal transduction pathways in porcine aortic endothelial cells","volume":"272","author":"Kroll","year":"1997","journal-title":"J. Biol. Chem."},{"key":"B112","doi-asserted-by":"publisher","first-page":"111","DOI":"10.1007\/s40272-020-00433-z","article-title":"Ranibizumab: a review in retinopathy of prematurity","volume":"23","author":"Lee","year":"2021","journal-title":"Paediatr. Drugs"},{"key":"B113","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1186\/s43556-022-00110-2","article-title":"Targeting the PI3K\/AKT\/mTOR and RAF\/MEK\/ERK pathways for cancer therapy","volume":"3","author":"Li","year":"","journal-title":"Mol. Biomed."},{"key":"B114","doi-asserted-by":"publisher","first-page":"842960","DOI":"10.3389\/fonc.2022.842960","article-title":"Novel angiogenic regulators and anti-angiogenesis drugs targeting angiogenesis signaling pathways: perspectives for targeting angiogenesis in lung cancer","volume":"12","author":"Li","year":"","journal-title":"Front. Oncol."},{"key":"B115","doi-asserted-by":"publisher","first-page":"332","DOI":"10.1016\/j.canlet.2015.11.015","article-title":"Encorafenib (LGX818), a potent BRAF inhibitor, induces senescence accompanied by autophagy in BRAFV600E melanoma cells","volume":"370","author":"Li","year":"2016","journal-title":"Cancer Lett."},{"key":"B116","doi-asserted-by":"publisher","first-page":"940","DOI":"10.1016\/j.jtho.2023.03.015","article-title":"D-1553 (garsorasib), a potent and selective inhibitor of KRAS(G12C) in patients with NSCLC: phase 1 study results","volume":"18","author":"Li","year":"2023","journal-title":"J. Thorac. Oncol."},{"key":"B117","doi-asserted-by":"publisher","first-page":"9424","DOI":"10.3390\/ijms23169424","article-title":"Aflibercept versus faricimab in the treatment of neovascular age-related macular degeneration and diabetic macular edema: a review","volume":"23","author":"Liberski","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B118","doi-asserted-by":"publisher","first-page":"e285","DOI":"10.1002\/mco2.285","article-title":"RAS-targeted cancer therapy: advances in drugging specific mutations","volume":"4","author":"Liu","year":"","journal-title":"MedComm"},{"key":"B119","doi-asserted-by":"publisher","first-page":"2319","DOI":"10.1158\/1535-7163.MCT-12-0993-T","article-title":"BAY 80-6946 is a highly selective intravenous PI3K inhibitor with potent p110\u03b1 and p110\u03b4 activities in tumor cell lines and xenograft models","volume":"12","author":"Liu","year":"2013","journal-title":"Mol. Cancer Ther."},{"key":"B120","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1016\/j.ejvs.2020.03.042","article-title":"Inhibition of phosphatidylinositol 3-kinase gamma by IPI-549 attenuates abdominal aortic aneurysm formation in mice","volume":"60","author":"Liu","year":"2020","journal-title":"Eur. J. Vasc. Endovasc. Surg."},{"key":"B121","doi-asserted-by":"publisher","first-page":"73","DOI":"10.1007\/s00249-018-1334-y","article-title":"Electrostatic mechanism of V600E mutation-induced B-Raf constitutive activation in colorectal cancer: molecular implications for the selectivity difference between type-I and type-II inhibitors","volume":"48","author":"Liu","year":"2019","journal-title":"Eur. Biophys. J."},{"key":"B122","doi-asserted-by":"publisher","first-page":"198","DOI":"10.1038\/s41392-023-01460-1","article-title":"Angiogenic signaling pathways and anti-angiogenic therapy for cancer","volume":"8","author":"Liu","year":"","journal-title":"Signal Transduct. Target Ther."},{"key":"B124","doi-asserted-by":"publisher","first-page":"16173","DOI":"10.1021\/acs.jmedchem.2c01438","article-title":"JDQ443, a structurally novel, pyrazole-based, covalent inhibitor of KRAS(G12C) for the treatment of solid tumors","volume":"65","author":"Lorthiois","year":"2022","journal-title":"J. Med. Chem."},{"key":"B125","doi-asserted-by":"publisher","first-page":"934963","DOI":"10.1155\/2015\/934963","article-title":"Antiproliferative, apoptotic, and autophagic activity of ranibizumab, bevacizumab, pegaptanib, and aflibercept on fibroblasts: implication for choroidal neovascularization","volume":"2015","author":"Lytvynchuk","year":"2015","journal-title":"J. Ophthalmol."},{"key":"B126","doi-asserted-by":"publisher","first-page":"15585","DOI":"10.3390\/ijms232415585","article-title":"The VEGF\/VEGFR Axis revisited: implications for cancer therapy","volume":"23","author":"Mabeta","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B127","doi-asserted-by":"publisher","first-page":"216","DOI":"10.1016\/j.canlet.2015.07.028","article-title":"Classical and non-classical proangiogenic factors as a target of antiangiogenic therapy in tumor microenvironment","volume":"380","author":"Marech","year":"2016","journal-title":"Cancer Lett."},{"key":"B128","doi-asserted-by":"publisher","first-page":"1249","DOI":"10.1007\/s40265-019-01161-6","article-title":"Alpelisib: first global approval","volume":"79","author":"Markham","year":"","journal-title":"Drugs"},{"key":"B129","doi-asserted-by":"publisher","first-page":"1997","DOI":"10.1007\/s40265-019-01231-9","article-title":"Brolucizumab: first approval","volume":"79","author":"Markham","year":"","journal-title":"Drugs"},{"key":"B130","doi-asserted-by":"publisher","first-page":"931","DOI":"10.1007\/s40265-020-01331-x","article-title":"Selumetinib: first approval","volume":"80","author":"Markham","year":"2020","journal-title":"Drugs"},{"key":"B131","doi-asserted-by":"publisher","first-page":"4806","DOI":"10.1158\/1078-0432.CCR-12-0742","article-title":"First-in-human, phase I dose-escalation study of the safety, pharmacokinetics, and pharmacodynamics of RO5126766, a first-in-class dual MEK\/RAF inhibitor in patients with solid tumors","volume":"18","author":"Martinez-Garcia","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"B132","doi-asserted-by":"publisher","first-page":"246","DOI":"10.1016\/j.ygyno.2014.12.019","article-title":"Phase II study of the PI3K inhibitor pilaralisib (SAR245408; XL147) in patients with advanced or recurrent endometrial carcinoma","volume":"136","author":"Matulonis","year":"2015","journal-title":"Gynecol. Oncol."},{"key":"B133","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1016\/j.bbcan.2018.08.001","article-title":"The next generation of PI3K-Akt-mTOR pathway inhibitors in breast cancer cohorts","volume":"1870","author":"Mckenna","year":"2018","journal-title":"Biochim. Biophys. Acta Rev. Cancer"},{"key":"B134","doi-asserted-by":"publisher","first-page":"20995","DOI":"10.1074\/jbc.M407060200","article-title":"Activation of p38 has opposing effects on the proliferation and migration of endothelial cells","volume":"280","author":"Mcmullen","year":"2005","journal-title":"J. Biol. Chem."},{"key":"B136","doi-asserted-by":"publisher","first-page":"1261","DOI":"10.1083\/jcb.200703052","article-title":"Newly identified biologically active and proteolysis-resistant VEGF-A isoform VEGF111 is induced by genotoxic agents","volume":"179","author":"Mineur","year":"2007","journal-title":"J. Cell Biol."},{"key":"B137","doi-asserted-by":"publisher","first-page":"503","DOI":"10.1093\/jjco\/hyy053","article-title":"Drug review: pazopanib","volume":"48","author":"Miyamoto","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"B138","doi-asserted-by":"publisher","first-page":"1877","DOI":"10.1093\/cvr\/cvaa291","article-title":"The physiological and pathological functions of VEGFR3 in cardiac and lymphatic development and related diseases","volume":"117","author":"Monaghan","year":"2021","journal-title":"Cardiovasc Res."},{"key":"B139","doi-asserted-by":"publisher","first-page":"683","DOI":"10.1358\/dot.2010.46.9.1516989","article-title":"Vandetanib: an overview of its clinical development in NSCLC and other tumors","volume":"46","author":"Morabito","year":"2010","journal-title":"Drugs Today (Barc)."},{"key":"B140","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1016\/j.ophtha.2006.05.070","article-title":"Systemic bevacizumab (Avastin) therapy for neovascular age-related macular degeneration: twenty-four-week results of an uncontrolled open-label clinical study","volume":"113","author":"Moshfeghi","year":"2006","journal-title":"Ophthalmology"},{"key":"B141","doi-asserted-by":"publisher","first-page":"670","DOI":"10.18502\/jovr.v16i4.9757","article-title":"Side effects of brolucizumab","volume":"16","author":"Motevasseli","year":"","journal-title":"J. Ophthalmic and Vis. Res."},{"key":"B142","doi-asserted-by":"publisher","first-page":"670","DOI":"10.18502\/jovr.v16i4.9757","article-title":"Side effects of brolucizumab","volume":"16","author":"Motevasseli","year":"","journal-title":"J. Ophthalmic Vis. Res."},{"key":"B143","doi-asserted-by":"publisher","first-page":"702","DOI":"10.1038\/nri3064","article-title":"The parallel lives of angiogenesis and immunosuppression: cancer and other tales","volume":"11","author":"Motz","year":"2011","journal-title":"Nat. Rev. Immunol."},{"key":"B144","doi-asserted-by":"publisher","first-page":"41","DOI":"10.1634\/theoncologist.2016-0197","article-title":"Sunitinib: ten years of successful clinical use and study in advanced renal cell carcinoma","volume":"22","author":"Motzer","year":"2017","journal-title":"Oncologist"},{"key":"B145","doi-asserted-by":"publisher","first-page":"2660","DOI":"10.1002\/art.11232","article-title":"Vegfb gene knockout mice display reduced pathology and synovial angiogenesis in both antigen-induced and collagen-induced models of arthritis","volume":"48","author":"Mould","year":"2003","journal-title":"Arthritis Rheum."},{"key":"B146","doi-asserted-by":"publisher","first-page":"995","DOI":"10.1038\/nrd1601","article-title":"Bevacizumab","volume":"3","author":"Muhsin","year":"2004","journal-title":"Nat. Rev. Drug Discov."},{"key":"B147","doi-asserted-by":"publisher","first-page":"925","DOI":"10.1007\/s12325-012-0060-6","article-title":"Cabozantinib for the treatment of advanced medullary thyroid cancer","volume":"29","author":"Nagilla","year":"2012","journal-title":"Adv. Ther."},{"key":"B148","doi-asserted-by":"publisher","first-page":"3395","DOI":"10.2147\/DDDT.S368963","article-title":"Spotlight on faricimab in the treatment of wet age-related macular degeneration: design, development and place in therapy","volume":"16","author":"Nair","year":"2022","journal-title":"Drug Des. Devel Ther."},{"key":"B149","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1038\/nrd1955","article-title":"Pegaptanib, a targeted anti-VEGF aptamer for ocular vascular disease","volume":"5","author":"Ng","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"B150","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1177\/1756287217748867","article-title":"Cabozantinib in the treatment of advanced renal cell carcinoma in adults following prior vascular endothelial growth factor targeted therapy: clinical trial evidence and experience","volume":"10","author":"Osanto","year":"2018","journal-title":"Ther. Adv. Urol."},{"key":"B151","doi-asserted-by":"publisher","first-page":"904","DOI":"10.1093\/carcin\/bgr052","article-title":"1'-Acetoxychavicol acetate suppresses angiogenesis-mediated human prostate tumor growth by targeting VEGF-mediated Src-FAK-Rho GTPase-signaling pathway","volume":"32","author":"Pang","year":"2011","journal-title":"Carcinogenesis"},{"key":"B152","doi-asserted-by":"publisher","first-page":"152","DOI":"10.1186\/s13045-022-01375-4","article-title":"Drugging KRAS: current perspectives and state-of-art review","volume":"15","author":"Parikh","year":"2022","journal-title":"J. Hematol. Oncol."},{"key":"B153","doi-asserted-by":"publisher","first-page":"103","DOI":"10.1021\/ml3003132","article-title":"Discovery and biological profiling of potent and selective mTOR inhibitor GDC-0349","volume":"4","author":"Pei","year":"2013","journal-title":"ACS Med. Chem. Lett."},{"key":"B154","doi-asserted-by":"publisher","first-page":"180","DOI":"10.1016\/j.ajo.2022.02.019","article-title":"A randomized, double-masked, multicenter trial of topical acrizanib (LHA510), a tyrosine kinase VEGF-receptor inhibitor, in treatment-experienced subjects with neovascular age-related macular degeneration","volume":"239","author":"Poor","year":"2022","journal-title":"Am. J. Ophthalmol."},{"key":"B155","doi-asserted-by":"publisher","first-page":"51","DOI":"10.18240\/ijo.2019.01.08","article-title":"One-year outcomes of intravitreal conbercept combined rescue therapy for polypoidal choroidal vasculopathy in a Chinese population: a real-life clinical data","volume":"12","author":"Qi","year":"2019","journal-title":"Int. J. Ophthalmol."},{"key":"B156","doi-asserted-by":"publisher","first-page":"6934","DOI":"10.3390\/ijms23136934","article-title":"Novel drugs with high efficacy against tumor angiogenesis","volume":"23","author":"Qi","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"B157","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1358\/dot.2020.56.11.3199812","article-title":"Brolucizumab as treatment of wet age-related maculopathy","volume":"56","author":"Rahman","year":"2020","journal-title":"Drugs Today (Barc)."},{"key":"B158","doi-asserted-by":"publisher","first-page":"1190","DOI":"10.1038\/onc.2009.403","article-title":"Sorafenib, a dual Raf kinase\/vascular endothelial growth factor receptor inhibitor has significant anti-myeloma activity and synergizes with common anti-myeloma drugs","volume":"29","author":"Ramakrishnan","year":"2010","journal-title":"Oncogene"},{"key":"B159","doi-asserted-by":"publisher","first-page":"185","DOI":"10.1007\/s10456-017-9552-y","article-title":"Anti-angiogenesis for cancer revisited: is there a role for combinations with immunotherapy?","volume":"20","author":"Ramjiawan","year":"2017","journal-title":"Angiogenesis"},{"key":"B160","doi-asserted-by":"publisher","first-page":"103557","DOI":"10.1016\/j.drudis.2023.103557","article-title":"Recent progress in targeting KRAS mutant cancers with covalent G12C-specific inhibitors","volume":"28","author":"Rathod","year":"2023","journal-title":"Drug Discov. Today"},{"key":"B161","doi-asserted-by":"publisher","first-page":"7","DOI":"10.3389\/fbioe.2018.00007","article-title":"Biology of vascular endothelial growth factor C in the morphogenesis of lymphatic vessels","volume":"6","author":"Rauniyar","year":"2018","journal-title":"Front. Bioeng. Biotechnol."},{"key":"B162","doi-asserted-by":"publisher","first-page":"1265","DOI":"10.15252\/emmm.201505889","article-title":"Targeting key angiogenic pathways with a bispecific CrossMAb optimized for neovascular eye diseases","volume":"8","author":"Regula","year":"2016","journal-title":"EMBO Mol. Med."},{"key":"B163","doi-asserted-by":"publisher","first-page":"671","DOI":"10.1038\/386671a0","article-title":"Mechanisms of angiogenesis","volume":"386","author":"Risau","year":"1997","journal-title":"Nature"},{"key":"B164","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/j.phrs.2018.08.013","article-title":"Targeting oncogenic Raf protein-serine\/threonine kinases in human cancers","volume":"135","author":"Roskoski","year":"2018","journal-title":"Pharmacol. Res."},{"key":"B165","doi-asserted-by":"publisher","first-page":"106552","DOI":"10.1016\/j.phrs.2022.106552","article-title":"Properties of FDA-approved small molecule protein kinase inhibitors: a 2023 update","volume":"187","author":"Roskoski","year":"2023","journal-title":"Pharmacol. Res."},{"key":"B166","doi-asserted-by":"publisher","first-page":"1053","DOI":"10.1021\/jm501562a","article-title":"Nintedanib: from discovery to the clinic","volume":"58","author":"Roth","year":"2015","journal-title":"J. Med. Chem."},{"key":"B167","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1080\/17474124.2016.1209407","article-title":"Apatinib for the treatment of gastric cancer","volume":"10","author":"Roviello","year":"2016","journal-title":"Expert Rev. Gastroenterol. Hepatol."},{"key":"B168","doi-asserted-by":"publisher","first-page":"338","DOI":"10.1177\/1756287216663073","article-title":"Cabozantinib in the treatment of advanced renal cell carcinoma: clinical trial evidence and experience","volume":"8","author":"Ruiz-Morales","year":"2016","journal-title":"Ther. Adv. Urol."},{"key":"B169","doi-asserted-by":"publisher","first-page":"619","DOI":"10.1517\/14656566.2013.770475","article-title":"Trametinib (GSK1120212) in the treatment of melanoma","volume":"14","author":"Salama","year":"2013","journal-title":"Expert Opin. Pharmacother."},{"key":"B170","doi-asserted-by":"publisher","first-page":"e0153052","DOI":"10.1371\/journal.pone.0153052","article-title":"Comparing the effectiveness of bevacizumab to ranibizumab in patients with exudative age-related macular degeneration the BRAMD study","volume":"11","author":"Schauwvlieghe","year":"2016","journal-title":"PLoS One"},{"key":"B171","doi-asserted-by":"publisher","first-page":"348","DOI":"10.1177\/1756287216663979","article-title":"Sunitinib in the treatment of metastatic renal cell carcinoma","volume":"8","author":"Schmid","year":"2016","journal-title":"Ther. Adv. Urol."},{"key":"B172","doi-asserted-by":"publisher","first-page":"914","DOI":"10.1136\/bjo.2008.144410","article-title":"Systemic bevacizumab (Avastin) therapy for exudative neovascular age-related macular degeneration. The BEAT-AMD-Study","volume":"93","author":"Schmid-Kubista","year":"2009","journal-title":"Br. J. Ophthalmol."},{"key":"B173","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1007\/s40265-018-0903-9","article-title":"Apatinib: a review in advanced gastric cancer and other advanced cancers","volume":"78","author":"Scott","year":"2018","journal-title":"Drugs"},{"key":"B174","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1016\/j.lungcan.2006.02.009","article-title":"Prognostic value of expression of vascular endothelial growth factor and its flt-1 and KDR receptors in stage I non-small-cell lung cancer","volume":"53","author":"Seto","year":"2006","journal-title":"Lung Cancer"},{"key":"B175","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1093\/jjco\/hyx144","article-title":"Safety and tolerability of selumetinib as a monotherapy, or in combination with docetaxel as second-line therapy, in Japanese patients with advanced solid malignancies or non-small cell lung cancer","volume":"48","author":"Seto","year":"2018","journal-title":"Jpn. J. Clin. Oncol."},{"key":"B176","doi-asserted-by":"publisher","first-page":"1162","DOI":"10.1177\/1060028015594813","article-title":"Idelalisib: a novel PI3K\u03b4 inhibitor for chronic lymphocytic leukemia","volume":"49","author":"Shah","year":"2015","journal-title":"Ann. Pharmacother."},{"key":"B177","doi-asserted-by":"publisher","first-page":"706","DOI":"10.18632\/oncotarget.23091","article-title":"The dual PI3K\/mTOR inhibitor dactolisib elicits anti-tumor activity in vitro and in vivo","volume":"9","author":"Shi","year":"2018","journal-title":"Oncotarget"},{"key":"B178","doi-asserted-by":"publisher","first-page":"1757","DOI":"10.1007\/s40265-018-0998-z","article-title":"Fruquintinib: first global approval","volume":"78","author":"Shirley","year":"2018","journal-title":"Drugs"},{"key":"B179","doi-asserted-by":"publisher","first-page":"825","DOI":"10.1007\/s40265-022-01713-3","article-title":"Faricimab: first approval","volume":"82","author":"Shirley","year":"2022","journal-title":"Drugs"},{"key":"B180","doi-asserted-by":"publisher","first-page":"130","DOI":"10.1002\/1878-0261.13031","article-title":"The PI3K\/mTOR inhibitor Gedatolisib eliminates dormant breast cancer cells in organotypic culture, but fails to prevent metastasis in preclinical settings","volume":"16","author":"Shor","year":"2022","journal-title":"Mol. Oncol."},{"key":"B181","doi-asserted-by":"publisher","first-page":"611","DOI":"10.1038\/nrm.2016.87","article-title":"Mechanisms and regulation of endothelial VEGF receptor signalling","volume":"17","author":"Simons","year":"2016","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"B182","first-page":"1324","article-title":"Pazopanib, a VEGF receptor tyrosine kinase inhibitor for cancer therapy","volume":"9","author":"Sloan","year":"2008","journal-title":"Curr. Opin. Investig. Drugs"},{"key":"B183","doi-asserted-by":"publisher","first-page":"2288","DOI":"10.1056\/NEJMoa1716948","article-title":"Atezolizumab for first-line treatment of metastatic nonsquamous NSCLC","volume":"378","author":"Socinski","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"B184","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1007\/s11912-007-0007-2","article-title":"Pazopanib: a novel multitargeted tyrosine kinase inhibitor","volume":"9","author":"Sonpavde","year":"2007","journal-title":"Curr. Oncol. Rep."},{"key":"B185","doi-asserted-by":"publisher","first-page":"2190","DOI":"10.1182\/blood-2014-03-559963","article-title":"The novel AKT inhibitor afuresertib shows favorable safety, pharmacokinetics, and clinical activity in multiple myeloma","volume":"124","author":"Spencer","year":"2014","journal-title":"Blood"},{"key":"B186","doi-asserted-by":"publisher","first-page":"186","DOI":"10.1038\/84635","article-title":"VEGF-D promotes the metastatic spread of tumor cells via the lymphatics","volume":"7","author":"Stacker","year":"2001","journal-title":"Nat. Med."},{"key":"B187","doi-asserted-by":"publisher","first-page":"1363","DOI":"10.1084\/jem.20111343","article-title":"VEGFR2 induces c-Src signaling and vascular permeability in vivo via the adaptor protein TSAd","volume":"209","author":"Sun","year":"2012","journal-title":"J. Exp. Med."},{"key":"B188","doi-asserted-by":"publisher","first-page":"131","DOI":"10.1016\/S0140-6736(21)00580-8","article-title":"Ipatasertib plus abiraterone and prednisolone in metastatic castration-resistant prostate cancer (IPATential150): a multicentre, randomised, double-blind, phase 3 trial","volume":"398","author":"Sweeney","year":"2021","journal-title":"Lancet"},{"key":"B189","doi-asserted-by":"publisher","first-page":"1057","DOI":"10.1007\/s40265-018-0939-x","article-title":"Anlotinib: first global approval","volume":"78","author":"Syed","year":"2018","journal-title":"Drugs"},{"key":"B190","doi-asserted-by":"publisher","first-page":"315","DOI":"10.1007\/s40265-020-01263-6","article-title":"Ramucirumab: a review in hepatocellular carcinoma","volume":"80","author":"Syed","year":"2020","journal-title":"Drugs"},{"key":"B191","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1159\/000513048","article-title":"Brolucizumab: a newly developed anti-VEGF molecule for the treatment of neovascular age-related macular degeneration","volume":"244","author":"Tadayoni","year":"2021","journal-title":"Ophthalmologica"},{"key":"B192","doi-asserted-by":"publisher","first-page":"2221","DOI":"10.1038\/sj.onc.1202527","article-title":"VEGF activates protein kinase C-dependent, but Ras-independent Raf-MEK-MAP kinase pathway for DNA synthesis in primary endothelial cells","volume":"18","author":"Takahashi","year":"1999","journal-title":"Oncogene"},{"key":"B193","doi-asserted-by":"publisher","first-page":"84","DOI":"10.3390\/jcm9010084","article-title":"Tumor angiogenesis and anti-angiogenic strategies for cancer treatment","volume":"9","author":"Teleanu","year":"2019","journal-title":"J. Clin. Med."},{"key":"B194","doi-asserted-by":"publisher","first-page":"849","DOI":"10.2146\/ajhp120253","article-title":"Vandetanib: a novel targeted therapy for the treatment of metastatic or locally advanced medullary thyroid cancer","volume":"70","author":"Ton","year":"2013","journal-title":"Am. J. Health Syst. Pharm."},{"key":"B195","doi-asserted-by":"publisher","first-page":"3041","DOI":"10.1073\/pnas.0711741105","article-title":"Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity","volume":"105","author":"Tsai","year":"2008","journal-title":"Proc. Natl. Acad. Sci. U. S. A."},{"key":"B196","doi-asserted-by":"publisher","first-page":"1107","DOI":"10.1080\/14740338.2016.1201060","article-title":"The safety of vandetanib for the treatment of thyroid cancer","volume":"15","author":"Tsang","year":"2016","journal-title":"Expert Opin. Drug Saf."},{"key":"B197","doi-asserted-by":"publisher","first-page":"1449","DOI":"10.1097\/IAE.0b013e3182278ab4","article-title":"A systematic review of the adverse events of intravitreal anti-vascular endothelial growth factor injections","volume":"31","author":"Van Der Reis","year":"2011","journal-title":"Retina-the J. Retin. Vitreous Dis."},{"key":"B198","doi-asserted-by":"publisher","first-page":"1692","DOI":"10.1158\/1541-7786.MCR-17-0026","article-title":"B-Cell receptor signaling regulates metabolism in chronic lymphocytic leukemia","volume":"15","author":"Vangapandu","year":"2017","journal-title":"Mol. Cancer Res."},{"key":"B199","doi-asserted-by":"publisher","first-page":"640","DOI":"10.3390\/diagnostics11040640","article-title":"Nephrotoxicity of anti-angiogenic therapies","volume":"11","author":"Van Wynsberghe","year":"2021","journal-title":"Diagnostics"},{"key":"B200","first-page":"616","article-title":"VEGF-C-VEGFR3\/Flt4 axis regulates mammary tumor growth and metastasis in an autocrine manner","volume":"5","author":"Varney","year":"2015","journal-title":"Am. J. Cancer Res."},{"key":"B201","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1177\/1078155216655474","article-title":"Evolution of ramucirumab in the treatment of cancer - a review of literature","volume":"23","author":"Vennepureddy","year":"2017","journal-title":"J. Oncol. Pharm. Pract."},{"key":"B202","doi-asserted-by":"publisher","first-page":"e113217","DOI":"10.1371\/journal.pone.0113217","article-title":"The dual RAF\/MEK inhibitor CH5126766\/RO5126766 may be a potential therapy for RAS-mutated tumor cells","volume":"9","author":"Wada","year":"2014","journal-title":"PLoS One"},{"key":"B203","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1016\/j.critrevonc.2016.06.009","article-title":"Therapeutic potential and critical analysis of trastuzumab and bevacizumab in combination with different chemotherapeutic agents against metastatic breast\/colorectal cancer affecting various endpoints","volume":"104","author":"Wahid","year":"2016","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"B204","doi-asserted-by":"publisher","first-page":"65","DOI":"10.1016\/j.ejmech.2019.02.069","article-title":"Structural studies of the binding of an antagonistic cyclic peptide to the VEGFR1 domain 2","volume":"169","author":"Wang","year":"2019","journal-title":"Eur. J. Med. Chem."},{"key":"B205","doi-asserted-by":"publisher","first-page":"734544","DOI":"10.3389\/fphar.2021.734544","article-title":"A cyclic peptide epitope of an under-explored VEGF-B loop 1 demonstrated in vivo anti-angiogenic and anti-tumor activities","volume":"12","author":"Wang","year":"2021","journal-title":"Front. Pharmacol."},{"key":"B206","doi-asserted-by":"publisher","first-page":"6598","DOI":"10.1021\/acs.jmedchem.7b00283","article-title":"Identification of peptidic antagonists of vascular endothelial growth factor receptor 1 by scanning the binding epitopes of its ligands","volume":"60","author":"Wang","year":"2017","journal-title":"J. Med. Chem."},{"key":"B207","doi-asserted-by":"publisher","first-page":"599281","DOI":"10.3389\/fcell.2020.599281","article-title":"Molecular bases of VEGFR-2-mediated physiological function and pathological role","volume":"8","author":"Wang","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"B208","doi-asserted-by":"publisher","first-page":"19897","DOI":"10.18632\/oncotarget.7658","article-title":"ZSTK474, a specific class I phosphatidylinositol 3-kinase inhibitor, induces G1 arrest and autophagy in human breast cancer MCF-7 cells","volume":"7","author":"Wang","year":"2016","journal-title":"Oncotarget"},{"key":"B209","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1038\/s41540-017-0037-9","article-title":"VEGFR1 promotes cell migration and proliferation through PLC gamma and PI3K pathways","volume":"3","author":"Weddell","year":"2017","journal-title":"Npj Syst. Biol. Appl."},{"key":"B210","doi-asserted-by":"publisher","first-page":"833","DOI":"10.1634\/theoncologist.2020-0292","article-title":"A phase ib study to evaluate the MEK inhibitor cobimetinib in combination with the ERK1\/2 inhibitor GDC-0994 in patients with advanced solid tumors","volume":"25","author":"Weekes","year":"2020","journal-title":"Oncologist"},{"key":"B211","doi-asserted-by":"publisher","first-page":"695","DOI":"10.1016\/s0092-8674(00)80456-0","article-title":"Crystal structure at 1.7 A resolution of VEGF in complex with domain 2 of the Flt-1 receptor","volume":"91","author":"Wiesmann","year":"1997","journal-title":"Cell"},{"key":"B212","doi-asserted-by":"publisher","first-page":"835","DOI":"10.1038\/nrd2130","article-title":"Discovery and development of sorafenib: a multikinase inhibitor for treating cancer","volume":"5","author":"Wilhelm","year":"2006","journal-title":"Nat. Rev. Drug Discov."},{"key":"B213","doi-asserted-by":"publisher","first-page":"245","DOI":"10.1002\/ijc.25864","article-title":"Regorafenib (BAY 73-4506): a new oral multikinase inhibitor of angiogenic, stromal and oncogenic receptor tyrosine kinases with potent preclinical antitumor activity","volume":"129","author":"Wilhelm","year":"2011","journal-title":"Int. J. Cancer"},{"key":"B214","doi-asserted-by":"publisher","first-page":"269","DOI":"10.1177\/2474126420930863","article-title":"Occlusive retinal vasculitis following intravitreal brolucizumab","volume":"4","author":"Witkin","year":"2020","journal-title":"J. Vitr. Dis."},{"key":"B215","doi-asserted-by":"publisher","first-page":"1245","DOI":"10.1007\/s40265-013-0096-1","article-title":"Trametinib: first global approval","volume":"73","author":"Wright","year":"2013","journal-title":"Drugs"},{"key":"B216","doi-asserted-by":"publisher","first-page":"20955","DOI":"10.1021\/jacs.2c09917","article-title":"Atroposelective negishi coupling optimization guided by multivariate linear regression analysis: asymmetric synthesis of KRAS G12C covalent inhibitor GDC-6036","volume":"144","author":"Xu","year":"2022","journal-title":"J. Am. Chem. Soc."},{"key":"B217","doi-asserted-by":"publisher","first-page":"933","DOI":"10.1126\/science.3263702","article-title":"Blocking of EGF-dependent cell proliferation by EGF receptor kinase inhibitors","volume":"242","author":"Yaish","year":"1988","journal-title":"Science"},{"key":"B218","doi-asserted-by":"publisher","first-page":"9753","DOI":"10.1021\/acs.jmedchem.3c00561","article-title":"Dimer peptide ligands of vascular endothelial growth factor: optimizing linker length for high affinity and antiangiogenic activity","volume":"66","author":"Ye","year":"2023","journal-title":"J. Med. Chem."},{"key":"B219","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/S2213-2600(16)30322-8","article-title":"Vandetanib in patients with previously treated RET-rearranged advanced non-small-cell lung cancer (LURET): an open-label, multicentre phase 2 trial","volume":"5","author":"Yoh","year":"2017","journal-title":"Lancet Respir. Med."},{"key":"B220","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1093\/annonc\/mdy461","article-title":"Biomarker analysis beyond angiogenesis: RAS\/RAF mutation status, tumour sidedness, and second-line ramucirumab efficacy in patients with metastatic colorectal carcinoma from RAISE-a global phase III study","volume":"30","author":"Yoshino","year":"2019","journal-title":"Ann. Oncol."},{"key":"B221","doi-asserted-by":"publisher","first-page":"1171","DOI":"10.1042\/bst0311171","article-title":"VEGF signalling: integration and multi-tasking in endothelial cell biology","volume":"31","author":"Zachary","year":"2003","journal-title":"Biochem. Soc. Trans."},{"key":"B222","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1358\/dot.2022.58.4.3400573","article-title":"Sotorasib: a treatment for non-small cell lung cancer with the KRAS G12C mutation","volume":"58","author":"Zheng","year":"2022","journal-title":"Drugs Today (Barc)."},{"key":"B223","doi-asserted-by":"publisher","first-page":"615","DOI":"10.1016\/j.exer.2006.02.010","article-title":"Pegaptanib for the treatment of age-related macular degeneration","volume":"83","author":"Zhou","year":"2006","journal-title":"Exp. Eye Res."}],"container-title":["Frontiers in Pharmacology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1307860\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,3]],"date-time":"2024-01-03T23:24:19Z","timestamp":1704324259000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fphar.2023.1307860\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,1,4]]},"references-count":222,"alternative-id":["10.3389\/fphar.2023.1307860"],"URL":"https:\/\/doi.org\/10.3389\/fphar.2023.1307860","relation":{},"ISSN":["1663-9812"],"issn-type":[{"value":"1663-9812","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,1,4]]},"article-number":"1307860"}}