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Angiogenesis, the formation of new blood vessels from pre-existing ones, is one of the major mechanisms to create this vascular network. Anti-angiogenic therapy was conceived as the inhibition of the cellular and molecular players involved in tumor angiogenesis such as vascular endothelial growth factor and its main receptors. Due to limitations of this therapy, different approaches of vessel modulation such as vascular normalization or vascular promotion have been studied showing benefits in different tumor models and clinical trials. In contrast to anti-angiogenic therapy, which inhibits the blood vessels that are being formed, vascular disruption therapy aims to destroy already formed tumor vessels. These malignant vascular structures differ from other blood vessels in terms of endothelial cell states, pericyte coverage and basement membrane development. The molecules used for vascular disruption are microtubule-binding molecules, flavonoids that induce endothelial cell apoptosis or molecules vectorized to endothelial receptors. Many vascular disruption agents have been tested in clinical trials showing some promising results, but with some limitations that include resistant rim cells or the development of hypoxia that induces cancer regrowth and poor delivery of the anti-tumor agents. The main objective of this review is to focus on vascular disruption agents therapy, novel molecules, new ways to overcome therapy resistance to them, current clinical status and, especially, the upcoming challenges and applications of these molecules.<\/jats:p>","DOI":"10.3390\/ijms262010085","type":"journal-article","created":{"date-parts":[[2025,10,16]],"date-time":"2025-10-16T16:33:22Z","timestamp":1760632402000},"page":"10085","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Vascular Disruption Therapy as a New Strategy for Cancer Treatment"],"prefix":"10.3390","volume":"26","author":[{"given":"Jes\u00fas","family":"G\u00f3mez-Escudero","sequence":"first","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0598-8167","authenticated-orcid":false,"given":"Patricia","family":"Berlana-Gal\u00e1n","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8076-4128","authenticated-orcid":false,"given":"Elena","family":"Guerra-Paes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0007-9173-0824","authenticated-orcid":false,"given":"Irene","family":"Torre-Cea","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-4332-6674","authenticated-orcid":false,"given":"Laura","family":"Marcos-Zazo","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-7094-7147","authenticated-orcid":false,"given":"Iv\u00e1n","family":"Carrera-Aguado","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-3436-9381","authenticated-orcid":false,"given":"Daniel","family":"C\u00e1ceres-Calle","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1687-5891","authenticated-orcid":false,"given":"Fernando","family":"S\u00e1nchez-Juanes","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Mu\u00f1oz-F\u00e9lix","sequence":"additional","affiliation":[{"name":"Departamento de Bioqu\u00edmica y Biolog\u00eda Molecular, Universidad de Salamanca, 37007 Salamanca, Spain"},{"name":"Instituto de Investigaci\u00f3n Biom\u00e9dica de Salamanca (IBSAL), 37007 Salamanca, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,10,16]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","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":"ref_2","doi-asserted-by":"crossref","first-page":"1359","DOI":"10.1038\/nm.2537","article-title":"Tumor Angiogenesis: Molecular Pathways and Therapeutic Targets","volume":"17","author":"Weis","year":"2011","journal-title":"Nat. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"R1161","DOI":"10.1016\/j.cub.2016.09.043","article-title":"Explosring Novel Methods for Modulating Tumor Blood Vessels in Cancer Treatment","volume":"26","author":"Wong","year":"2016","journal-title":"Curr. Biol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1071","DOI":"10.1152\/physrev.00038.2010","article-title":"Normalization of the Vasculature for Treatment of Cancer and Other Diseases","volume":"91","author":"Goel","year":"2011","journal-title":"Physiol. Rev."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"173692","DOI":"10.1016\/j.ejphar.2020.173692","article-title":"Vascular Disrupting Agents in Cancer Therapy","volume":"891","author":"Smolarczyk","year":"2021","journal-title":"Eur. J. Pharmacol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"114138","DOI":"10.1016\/j.addr.2022.114138","article-title":"Destruction of Tumor Vasculature by Vascular Disrupting Agents in Overcoming the Limitation of EPR Effect","volume":"183","author":"Liu","year":"2022","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1021","DOI":"10.1002\/jcb.20783","article-title":"Vascular Disrupting Agents","volume":"99","author":"Pilat","year":"2006","journal-title":"J. Cell. Biochem."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1158\/1078-0432.CCR-0642-03","article-title":"Vascular Targeting Agents as Cancer Therapeutics","volume":"10","author":"Thorpe","year":"2004","journal-title":"Clin. Cancer Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"612","DOI":"10.1634\/theoncologist.2008-0287","article-title":"Vascular Disrupting Agents: A Novel Mechanism of Action in the Battle Against Non-Small Cell Lung Cancer","volume":"14","author":"Gridelli","year":"2009","journal-title":"Oncologist"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"15444","DOI":"10.18632\/oncotarget.6999","article-title":"Tumor Resistance to Vascular Disrupting Agents: Mechanisms, Imaging, and Solutions","volume":"7","author":"Liang","year":"2016","journal-title":"Oncotarget"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/s41568-024-00736-0","article-title":"Targeting the Tumour Vasculature: From Vessel Destruction to Promotion","volume":"24","author":"Guelfi","year":"2024","journal-title":"Nat. Rev. Cancer"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Kr\u00fcger-Genge, A., Blocki, A., Franke, R.-P., and Jung, F. (2019). Vascular Endothelial Cell Biology: An Update. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184411"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1016\/j.semcancer.2009.05.003","article-title":"The Angiogenic Switch in Carcinogenesis","volume":"19","author":"Baeriswyl","year":"2009","journal-title":"Semin. Cancer Biol."},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Paulsen, E.-E., Andersen, S., Rakaee, M., Pedersen, M.I., Lombardi, A.P., P\u00f8hl, M., Kilvaer, T., Busund, L.-T., Pezzella, F., and Donnem, T. (2023). Impact of Microvessel Patterns and Immune Status in NSCLC: A Non-Angiogenic Vasculature Is an Independent Negative Prognostic Factor in Lung Adenocarcinoma. Front. Oncol., 13.","DOI":"10.3389\/fonc.2023.1157461"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1007\/s10456-017-9562-9","article-title":"Tumor Angiogenesis and Vascular Normalization: Alternative Therapeutic Targets","volume":"20","author":"Viallard","year":"2017","journal-title":"Angiogenesis"},{"key":"ref_16","doi-asserted-by":"crossref","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":"2023","journal-title":"Signal Transduct. Target. Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"323","DOI":"10.1038\/nrc.2018.14","article-title":"Non-Angiogenic Tumours and Their Influence on Cancer Biology","volume":"18","author":"Donnem","year":"2018","journal-title":"Nat. Rev. Cancer"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1016\/j.addr.2011.04.002","article-title":"Role of Tumor Vascular Architecture in Drug Delivery","volume":"63","author":"Narang","year":"2011","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1038\/nm0901-987","article-title":"Normalizing Tumor Vasculature with Anti-Angiogenic Therapy: A New Paradigm for Combination Therapy","volume":"7","author":"Jain","year":"2001","journal-title":"Nat. Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1002\/ar.1092280107","article-title":"A Novel Mechanism of Capillary Growth in the Rat Pulmonary Microcirculation","volume":"228","author":"Burri","year":"1990","journal-title":"Anat. Rec."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1016\/j.canlet.2011.10.040","article-title":"Intussusceptive Microvascular Growth in Tumors","volume":"316","author":"Ribatti","year":"2012","journal-title":"Cancer Lett."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000448551","article-title":"Vasculogenesis and Its Cellular Therapeutic Applications","volume":"203","author":"Ratajska","year":"2017","journal-title":"Cells Tissues Organs"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Liu, X., Zhang, J., Yi, T., Li, H., Tang, X., Liu, D., Wu, D., and Li, Y. (2025). Decoding Tumor Angiogenesis: Pathways, Mechanisms, and Future Directions in Anti-Cancer Strategies. Biomark. Res., 13.","DOI":"10.1186\/s40364-025-00779-x"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"55","DOI":"10.1007\/s10456-019-09698-6","article-title":"Vessel Co-Option and Resistance to Anti-Angiogenic Therapy","volume":"23","author":"Kuczynski","year":"2020","journal-title":"Angiogenesis"},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Maishi, N., Annan, D.A., Kikuchi, H., Hida, Y., and Hida, K. (2019). Tumor Endothelial Heterogeneity in Cancer Progression. Cancers, 11.","DOI":"10.3390\/cancers11101511"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2018","DOI":"10.1016\/j.apsb.2020.09.014","article-title":"Manipulation of Immune\u2013Vascular Crosstalk: New Strategies towards Cancer Treatment","volume":"10","author":"Zhao","year":"2020","journal-title":"Acta Pharm. Sin. B"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nrd3455","article-title":"Principles and Mechanisms of Vessel Normalization for Cancer and Other Angiogenic Diseases","volume":"10","author":"Carmeliet","year":"2011","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"5223","DOI":"10.7150\/thno.84947","article-title":"Visualizing Vasculature and Its Response to Therapy in the Tumor Microenvironment","volume":"13","author":"Lin","year":"2023","journal-title":"Theranostics"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1002\/jcb.21187","article-title":"Tumor Microenvironment Abnormalities: Causes, Consequences, and Strategies to Normalize","volume":"101","author":"Fukumura","year":"2007","journal-title":"J. Cell. Biochem."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Matuszewska, K., Pereira, M., Petrik, D., Lawler, J., and Petrik, J. (2021). Normalizing Tumor Vasculature to Reduce Hypoxia, Enhance Perfusion, and Optimize Therapy Uptake. Cancers, 13.","DOI":"10.3390\/cancers13174444"},{"key":"ref_31","doi-asserted-by":"crossref","unstructured":"Tzeng, H.-T., and Huang, Y.-J. (2023). Tumor Vasculature as an Emerging Pharmacological Target to Promote Anti-Tumor Immunity. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24054422"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"613","DOI":"10.1016\/j.tips.2019.07.001","article-title":"Tumor Vasculatures: A New Target for Cancer Immunotherapy","volume":"40","author":"Liu","year":"2019","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/s41419-017-0061-0","article-title":"Defining the Role of the Tumor Vasculature in Antitumor Immunity and Immunotherapy","volume":"9","author":"Schaaf","year":"2018","journal-title":"Cell Death Dis."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"288","DOI":"10.1016\/0026-2862(86)90018-X","article-title":"Microvascular Permeability of Normal and Neoplastic Tissues","volume":"31","author":"Gerlowski","year":"1986","journal-title":"Microvasc. Res."},{"key":"ref_35","first-page":"3752","article-title":"Vascular Permeability in a Human Tumor Xenograft: Molecular Size Dependence and Cutoff Size1","volume":"55","author":"Yuan","year":"1995","journal-title":"Cancer Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"3731","DOI":"10.1158\/0008-5472.CAN-04-0074","article-title":"Vascular Normalization by Vascular Endothelial Growth Factor Receptor 2 Blockade Induces a Pressure Gradient Across the Vasculature and Improves Drug Penetration in Tumors","volume":"64","author":"Tong","year":"2004","journal-title":"Cancer Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1126\/science.1104819","article-title":"Normalization of Tumor Vasculature: An Emerging Concept in Antiangiogenic Therapy","volume":"307","author":"Jain","year":"2005","journal-title":"Science"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1007\/s10456-014-9420-y","article-title":"Anti-Angiogenic Therapy for Cancer: Current Progress, Unresolved Questions and Future Directions","volume":"17","author":"Vasudev","year":"2014","journal-title":"Angiogenesis"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"2335","DOI":"10.1056\/NEJMoa032691","article-title":"Bevacizumab plus Irinotecan, Fluorouracil, and Leucovorin for Metastatic Colorectal Cancer","volume":"350","author":"Hurwitz","year":"2004","journal-title":"N. Engl. J. Med."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"592","DOI":"10.1038\/nrc2442","article-title":"Modes of Resistance to Anti-Angiogenic Therapy","volume":"8","author":"Bergers","year":"2008","journal-title":"Nat. Rev. Cancer"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"362","DOI":"10.1002\/path.4845","article-title":"Vessel Co-Option Is Common in Human Lung Metastases and Mediates Resistance to Anti-Angiogenic Therapy in Preclinical Lung Metastasis Models: Vessel Co-Option in Lung Metastases","volume":"241","author":"Bridgeman","year":"2017","journal-title":"J. Pathol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"465","DOI":"10.1038\/nrclinonc.2009.94","article-title":"Adverse Effects of Anticancer Agents That Target the VEGF Pathway","volume":"6","author":"Chen","year":"2009","journal-title":"Nat. Rev. Clin. Oncol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1227","DOI":"10.1200\/JCO.2007.14.5466","article-title":"Phase III Trial of Cisplatin Plus Gemcitabine with Either Placebo or Bevacizumab As First-Line Therapy for Nonsquamous Non\u2013Small-Cell Lung Cancer: AVAiL","volume":"27","author":"Reck","year":"2009","journal-title":"J. Clin. Oncol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3191","DOI":"10.1200\/JCO.2009.27.7723","article-title":"Capecitabine, Bevacizumab, and Mitomycin in First-Line Treatment of Metastatic Colorectal Cancer: Results of the Australasian Gastrointestinal Trials Group Randomized Phase III MAX Study","volume":"28","author":"Tebbutt","year":"2010","journal-title":"J. Clin. Oncol."},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Zheng, W., Qian, C., Tang, Y., Yang, C., Zhou, Y., Shen, P., Chen, W., Yu, S., Wei, Z., and Wang, A. (2022). Manipulation of the Crosstalk between Tumor Angiogenesis and Immunosuppression in the Tumor Microenvironment: Insight into the Combination Therapy of Anti-Angiogenesis and Immune Checkpoint Blockade. Front. Immunol., 13.","DOI":"10.3389\/fimmu.2022.1035323"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2943","DOI":"10.1158\/0008-5472.CAN-12-4354","article-title":"Vascular Normalization as an Emerging Strategy to Enhance Cancer Immunotherapy","volume":"73","author":"Huang","year":"2013","journal-title":"Cancer Res."},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Swamy, K. (2022). Vascular Normalization and Immunotherapy: Spawning a Virtuous Cycle. Front. Oncol., 12.","DOI":"10.3389\/fonc.2022.1002957"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1016\/j.jtho.2021.09.014","article-title":"IMpower150 Final Exploratory Analyses for Atezolizumab Plus Bevacizumab and Chemotherapy in Key NSCLC Patient Subgroups With EGFR Mutations or Metastases in the Liver or Brain","volume":"17","author":"Nogami","year":"2022","journal-title":"J. Thorac. Oncol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1109","DOI":"10.1016\/S1470-2045(19)30458-9","article-title":"Ramucirumab plus Pembrolizumab in Patients with Previously Treated Advanced Non-Small-Cell Lung Cancer, Gastro-Oesophageal Cancer, or Urothelial Carcinomas (JVDF): A Multicohort, Non-Randomised, Open-Label, Phase 1a\/b Trial","volume":"20","author":"Herbst","year":"2019","journal-title":"Lancet Oncol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e20230025","DOI":"10.1002\/INMD.20230025","article-title":"Anti-angiogenic Therapy Enhances Cancer Immunotherapy: Mechanism and Clinical Application","volume":"2","author":"Li","year":"2024","journal-title":"Interdiscip. Med."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"eaak9670","DOI":"10.1126\/scitranslmed.aak9670","article-title":"Dual Angiopoietin-2 and VEGFA Inhibition Elicits Antitumor Immunity That Is Enhanced by PD-1 Checkpoint Blockade","volume":"9","author":"Schmittnaegel","year":"2017","journal-title":"Sci. Transl. Med."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"809","DOI":"10.1016\/j.trecan.2017.10.002","article-title":"Reprogramming Tumor Blood Vessels for Enhancing Immunotherapy","volume":"3","author":"Schmittnaegel","year":"2017","journal-title":"Trends Cancer"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"953","DOI":"10.1016\/j.ccell.2016.10.018","article-title":"Normalization of Tumor Vessels by Tie2 Activation and Ang2 Inhibition Enhances Drug Delivery and Produces a Favorable Tumor Microenvironment","volume":"30","author":"Park","year":"2016","journal-title":"Cancer Cell"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.ccell.2014.10.015","article-title":"Dual-Action Combination Therapy Enhances Angiogenesis While Reducing Tumor Growth and Spread","volume":"27","author":"Wong","year":"2015","journal-title":"Cancer Cell"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/nm.1941","article-title":"Stimulation of Tumor Growth and Angiogenesis by Low Concentrations of RGD-Mimetic Integrin Inhibitors","volume":"15","author":"Reynolds","year":"2009","journal-title":"Nat. Med."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"2072","DOI":"10.1016\/j.celrep.2017.07.080","article-title":"Lysophosphatidic Acid Receptor 4 Activation Augments Drug Delivery in Tumors by Tightening Endothelial Cell-Cell Contact","volume":"20","author":"Takara","year":"2017","journal-title":"Cell Rep."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1334","DOI":"10.1111\/cas.12488","article-title":"Eribulin Mesylate Reduces Tumor Microenvironment Abnormality by Vascular Remodeling in Preclinical Human Breast Cancer Models","volume":"105","author":"Funahashi","year":"2014","journal-title":"Cancer Sci."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"63","DOI":"10.1016\/j.ctrv.2010.05.001","article-title":"The Unique Characteristics of Tumor Vasculature and Preclinical Evidence for Its Selective Disruption by Tumor-Vascular Disrupting Agents","volume":"37","author":"Siemann","year":"2011","journal-title":"Cancer Treat. Rev."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"S12","DOI":"10.1259\/bjr\/36205483","article-title":"Tumour Vascular Disrupting Agents: Combating Treatment Resistance","volume":"81","author":"Tozer","year":"2008","journal-title":"Br. J. Radiol."},{"key":"ref_60","doi-asserted-by":"crossref","unstructured":"Newport, E.L., Pedrosa, A.R., Njegic, A., Hodivala-Dilke, K.M., and Mu\u00f1oz-F\u00e9lix, J.M. (2021). Improved Immunotherapy Efficacy by Vascular Modulation. Cancers, 13.","DOI":"10.3390\/cancers13205207"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1801","DOI":"10.1016\/S0002-9440(10)63540-7","article-title":"Abnormalities of Basement Membrane on Blood Vessels and Endothelial Sprouts in Tumors","volume":"163","author":"Baluk","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"1159","DOI":"10.1038\/sj.bjc.6603694","article-title":"Vascular Disrupting Agents in Clinical Development","volume":"96","author":"Hinnen","year":"2007","journal-title":"Br. J. Cancer"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"2491","DOI":"10.1002\/cncr.20299","article-title":"Vascular-targeting Therapies for Treatment of Malignant Disease","volume":"100","author":"Siemann","year":"2004","journal-title":"Cancer"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1038\/cdd.2009.176","article-title":"Mitotic Arrest and JNK-Induced Proteasomal Degradation of FLIP and Mcl-1 Are Key Events in the Sensitization of Breast Tumor Cells to TRAIL by Antimicrotubule Agents","volume":"17","year":"2010","journal-title":"Cell Death Differ."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"5692","DOI":"10.1182\/blood-2010-12-323857","article-title":"A Novel Vascular Disrupting Agent Plinabulin Triggers JNK-Mediated Apoptosis and Inhibits Angiogenesis in Multiple Myeloma Cells","volume":"117","author":"Singh","year":"2011","journal-title":"Blood"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"443","DOI":"10.1016\/j.clon.2007.03.014","article-title":"Vascular Damaging Agents","volume":"19","author":"Patterson","year":"2007","journal-title":"Clin. Oncol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.3109\/0284186X.2013.825050","article-title":"Induction of Hypoxia by Vascular Disrupting Agents and the Significance for Their Combination with Radiation Therapy","volume":"52","author":"Iversen","year":"2013","journal-title":"Acta Oncol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1016\/j.pharmthera.2019.06.001","article-title":"Vascular Disrupting Agents in Cancer Treatment: Cardiovascular Toxicity and Implications for Co-Administration with Other Cancer Chemotherapeutics","volume":"202","author":"Gill","year":"2019","journal-title":"Pharmacol. Ther."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"2105254","DOI":"10.1002\/adma.202105254","article-title":"Enzymatically Transformable Polymersome-Based Nanotherapeutics to Eliminate Minimal Relapsable Cancer","volume":"33","author":"Li","year":"2021","journal-title":"Adv. Mater."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1683","DOI":"10.1021\/mp300505w","article-title":"Nanoparticle Delivered Vascular Disrupting Agents (VDAs): Use of TNF-Alpha Conjugated Gold Nanoparticles for Multimodal Cancer Therapy","volume":"10","author":"Shenoi","year":"2013","journal-title":"Mol. Pharm."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"21381","DOI":"10.1021\/acsami.9b05536","article-title":"Integrated Hydrogel Platform for Programmed Antitumor Therapy Based on Near Infrared-Triggered Hyperthermia and Vascular Disruption","volume":"11","author":"Liang","year":"2019","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"7160","DOI":"10.1039\/D3TB00807J","article-title":"An Erythrocyte Membrane-Modified Biomimetic Synergistic Nanosystem for Cancer Anti-Vascular Therapy and Initial Efficacy Monitoring","volume":"11","author":"Zhang","year":"2023","journal-title":"J. Mater. Chem. B"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"79ra33","DOI":"10.1126\/scitranslmed.3001963","article-title":"The Fate and Toxicity of Raman-Active Silica-Gold Nanoparticles in Mice","volume":"3","author":"Thakor","year":"2011","journal-title":"Sci. Transl. Med."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"253","DOI":"10.7150\/thno.16681","article-title":"Enhancing Nanoparticle Accumulation and Retention in Desmoplastic Tumors via Vascular Disruption for Internal Radiation Therapy","volume":"7","author":"Satterlee","year":"2017","journal-title":"Theranostics"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"2348","DOI":"10.1021\/acs.bioconjchem.2c00418","article-title":"Engineering and Validation of a Peptide-Stabilized Poly(Lactic- Co -Glycolic) Acid Nanoparticle for Targeted Delivery of a Vascular Disruptive Agent in Cancer Therapy","volume":"33","author":"Dragulska","year":"2022","journal-title":"Bioconjug. Chem."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Sidorenko, V., Scodeller, P., Uustare, A., Ogibalov, I., Tasa, A., Tshubrik, O., Salum\u00e4e, L., Sugahara, K.N., Sim\u00f3n-Gracia, L., and Teesalu, T. (2024). Targeting Vascular Disrupting Agent-Treated Tumor Microenvironment with Tissue-Penetrating Nanotherapy. Sci. Rep., 14.","DOI":"10.1038\/s41598-024-64610-7"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"1348","DOI":"10.2174\/0929867322666150114163732","article-title":"Tubulin Colchicine Binding Site Inhibitors as Vascular Disrupting Agents in Clinical Developments","volume":"22","author":"Ji","year":"2015","journal-title":"Curr. Med. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"101969","DOI":"10.1016\/j.xcrm.2025.101969","article-title":"First-in-Human Phase 1 Study of an Orally Bioavailable Vascular-Disrupting Agent DX1002 in Patients with Advanced Solid Tumors","volume":"6","author":"Wei","year":"2025","journal-title":"Cell Rep. Med."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Prieto, L., Gavi\u00f1a, D., Escolano, M., C\u00e1novas-Belch\u00ed, M., S\u00e1nchez-Rosell\u00f3, M., Del Pozo, C., Falomir, E., and D\u00edaz-Oltra, S. (2025). Synthesis and Biological Evaluation of New Cis-Restricted Triazole Analogues of Combretastatin A-4. Molecules, 30.","DOI":"10.3390\/molecules30020317"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"605","DOI":"10.1016\/j.bmc.2006.10.020","article-title":"Vascular Disrupting Agents","volume":"15","author":"Lippert","year":"2007","journal-title":"Bioorg. Med. Chem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"1415","DOI":"10.1158\/1078-0432.CCR-11-2414","article-title":"Phase I Clinical and Pharmacokinetic Evaluation of the Vascular-Disrupting Agent OXi4503 in Patients with Advanced Solid Tumors","volume":"18","author":"Patterson","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.actbio.2017.02.001","article-title":"A Poly(l-Glutamic Acid)-Combretastatin A4 Conjugate for Solid Tumor Therapy: Markedly Improved Therapeutic Efficiency through Its Low Tissue Penetration in Solid Tumor","volume":"53","author":"Liu","year":"2017","journal-title":"Acta Biomater."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"591","DOI":"10.1016\/j.actbio.2025.07.055","article-title":"Quaternary Ammonium Salt Microspheres Loaded with Vascular Disrupting Agents for Targeted Interventional Therapy of Hepatocellular Carcinoma","volume":"203","author":"Su","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Li, J., Li, Z., and Wang, K. (2025). Targeting Angiogenesis in Gastrointestinal Tumors: Strategies from Vascular Disruption to Vascular Normalization and Promotion Strategies Angiogenesis Strategies in GI Tumor Therapy. Front. Immunol., 16.","DOI":"10.3389\/fimmu.2025.1550752"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Chu, H., Xu, Y., Shan, Y., Sun, M., Zhao, W., Fang, X., Shen, N., and Tang, Z. (2025). Platelet Hitchhiking Vascular-Disrupting Agents for Self-Amplified Tumor-Targeting Therapy. J. Nanobiotechnology, 23.","DOI":"10.1186\/s12951-025-03262-9"},{"key":"ref_86","doi-asserted-by":"crossref","unstructured":"Endo, R., Ueda, T., Nagaoki, T., Sato, Y., Maishi, N., Hida, K., Harashima, H., and Nakamura, T. (2025). Selective Vascular Disrupting Therapy by Lipid Nanoparticle-Mediated Fas Ligand Silencing and Stimulation of STING. Biomaterials, 321.","DOI":"10.1016\/j.biomaterials.2025.123297"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"S1326","DOI":"10.1016\/j.annonc.2021.08.2127","article-title":"LBA48 DUBLIN-3 (BPI-2358-103): A Global Phase (Ph) III Trial with the Plinabulin\/Docetaxel (Plin\/Doc) Combination vs. Doc in 2nd\/3rd Line NSCLC Patients (Pts) with EGFR-Wild Type (Wt) Progressing on a Prior Platinum-Based Regimen","volume":"32","author":"Han","year":"2021","journal-title":"Ann. Oncol."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"9090","DOI":"10.1200\/JCO.2022.40.16_suppl.9090","article-title":"Subgroup Analysis in Patients (Pts) with Non-Squamous (N-Sq), EGFR-Wild Type (Wt), Second\/Third-Line NSCLC from the Global Phase (Ph) 3 Trial DUBLIN-3 (BPI-2358-103) with the Plinabulin\/Docetaxel (Plin\/Doc) Combination versus Doc Alone","volume":"40","author":"Han","year":"2022","journal-title":"J. Clin. Oncol."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1182\/blood-2020-141110","article-title":"Protective-2 (BPI-2358-106): A Confirmatory Trial to Demonstrate Superiority of the Plinabulin+Pegfilgrastim (Plin\/Peg) Combination Versus Standard of Care Pegfilgrastim for the Prevention of Chemotherapy-Induced Neutropenia (CIN) in Breast Cancer (BC) Patients (Pts)","volume":"136","author":"Blayney","year":"2020","journal-title":"Blood"},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1547","DOI":"10.1517\/13543784.17.10.1547","article-title":"ASA404: Update on Drug Development","volume":"17","author":"Rehman","year":"2008","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"996","DOI":"10.1111\/cbdd.13166","article-title":"An Overview on Vadimezan (DMXAA): The Vascular Disrupting Agent","volume":"91","author":"Seidi","year":"2018","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"8996","DOI":"10.1073\/pnas.90.19.8996","article-title":"Eradication of Large Solid Tumors in Mice with an Immunotoxin Directed against Tumor Vasculature","volume":"90","author":"Burrows","year":"1993","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_93","first-page":"371","article-title":"Induction of Lasting Complete Regression of Preformed Distinct Solid Tumors by Targeting the Tumor Vasculature Using Two New Anti-Endoglin Monoclonal Antibodies1","volume":"5","author":"Matsuno","year":"1999","journal-title":"Clin. Cancer Res."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"135","DOI":"10.2174\/156720111793663570","article-title":"Endoglin-Targeted Cancer Therapy","volume":"8","author":"Seon","year":"2011","journal-title":"Curr. Drug Deliv."},{"key":"ref_95","first-page":"4646","article-title":"Infarction of Solid Hodgkin\u2019s Tumors in Mice by Antibody-Directed Targeting of Tissue Factor to Tumor Vasculature1","volume":"58","author":"Ran","year":"1998","journal-title":"Cancer Res."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"e2424730122","DOI":"10.1073\/pnas.2424730122","article-title":"Embryonic Reprogramming of the Tumor Vasculature Reveals Targets for Cancer Therapy","volume":"122","author":"Huijbers","year":"2025","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"303","DOI":"10.1016\/j.yexmp.2017.02.005","article-title":"Endothelial Cell Markers from Clinician\u2019s Perspective","volume":"102","author":"Rakocevic","year":"2017","journal-title":"Exp. Mol. Pathol."},{"key":"ref_98","first-page":"167","article-title":"Markers of Endothelial Cells in Normal and Pathological Conditions","volume":"14","author":"Goncharov","year":"2020","journal-title":"Biochem. Mosc. Suppl. Ser. Membr. Cell Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1111\/cas.16045","article-title":"CD40 Is Expressed in the Subsets of Endothelial Cells Undergoing Partial Endothelial\u2013Mesenchymal Transition in Tumor Microenvironment","volume":"115","author":"Takahashi","year":"2024","journal-title":"Cancer Sci."},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"100038","DOI":"10.1016\/j.modpat.2022.100038","article-title":"Identifying SOX17 as a Sensitive and Specific Marker for Ovarian and Endometrial Carcinomas","volume":"36","author":"Shaker","year":"2023","journal-title":"Mod. Pathol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"1032","DOI":"10.1038\/12469","article-title":"Anti-Cancer Activity of Targeted pro-Apoptotic Peptides","volume":"5","author":"Ellerby","year":"1999","journal-title":"Nat. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"801","DOI":"10.18388\/abp.2006_3309","article-title":"Antitumor Effect of RGD-4C-GG-D(KLAKLAK)2 Peptide in Mouse B16(F10) Melanoma Model","volume":"53","author":"Smolarczyk","year":"2006","journal-title":"Acta Biochim. Pol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"469","DOI":"10.5483\/BMBRep.2006.39.5.469","article-title":"Differential Roles of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Angiogenesis","volume":"39","author":"Shibuya","year":"2006","journal-title":"BMB Rep."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"252","DOI":"10.4149\/neo_2018_180722N513","article-title":"Fusion Protein tTF-EG3287 Induces Occlusion of Tumor Vessels and Impairs Tumor Growth in Human Colon Cancer","volume":"66","author":"Qiu","year":"2019","journal-title":"Neoplasma"},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"284","DOI":"10.1111\/j.1365-2613.2009.00651.x","article-title":"Microtubule Depolymerizing Vascular Disrupting Agents: Novel Therapeutic Agents for Oncology and Other Pathologies","volume":"90","author":"Kanthou","year":"2009","journal-title":"Int. J. Exp. Pathol."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"799","DOI":"10.1016\/j.ejca.2005.01.001","article-title":"Tumour Parameters Affected by Combretastatin A-4 Phosphate Therapy in a Human Colorectal Xenograft Model in Nude Mice","volume":"41","author":"Boxer","year":"2005","journal-title":"Eur. J. Cancer"},{"key":"ref_107","doi-asserted-by":"crossref","unstructured":"Seidi, K., Jahanban-Esfahlan, R., and Zarghami, N. (2017). Tumor Rim Cells: From Resistance to Vascular Targeting Agents to Complete Tumor Ablation. Tumor Biol., 39.","DOI":"10.1177\/1010428317691001"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.jfma.2012.09.017","article-title":"Mechanisms of Tumor Resistance to Small-Molecule Vascular Disrupting Agents: Treatment and Rationale of Combination Therapy","volume":"112","author":"Wu","year":"2013","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"6191","DOI":"10.1021\/acs.nanolett.0c02515","article-title":"Spatiotemporally Targeted Nanomedicine Overcomes Hypoxia-Induced Drug Resistance of Tumor Cells after Disrupting Neovasculature","volume":"20","author":"Chen","year":"2020","journal-title":"Nano Lett."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"3689","DOI":"10.1172\/JCI94258","article-title":"Pericyte-Targeting Prodrug Overcomes Tumor Resistance to Vascular Disrupting Agents","volume":"127","author":"Chen","year":"2017","journal-title":"J. Clin. Investig."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/S0002-9440(10)63809-6","article-title":"Tumor Vessel Development and Maturation Impose Limits on the Effectiveness of Anti-Vascular Therapy","volume":"162","author":"Gee","year":"2003","journal-title":"Am. J. Pathol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"2906","DOI":"10.1182\/blood-2011-01-331694","article-title":"Pericytes Promote Endothelial Cell Survival through Induction of Autocrine VEGF-A Signaling and Bcl-w Expression","volume":"118","author":"Franco","year":"2011","journal-title":"Blood"},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"11187","DOI":"10.1021\/acs.jmedchem.2c00681","article-title":"Discovery of a Novel Vascular Disrupting Agent Inhibiting Tubulin Polymerization and HDACs with Potent Antitumor Effects","volume":"65","author":"Zhu","year":"2022","journal-title":"J. Med. Chem."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1016\/j.canlet.2018.01.016","article-title":"A Vascular Disrupting Agent Overcomes Tumor Multidrug Resistance by Skewing Macrophage Polarity toward the M1 Phenotype","volume":"418","author":"Lei","year":"2018","journal-title":"Cancer Lett."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"1969","DOI":"10.1172\/JCI44562","article-title":"TIE2-Expressing Macrophages Limit the Therapeutic Efficacy of the Vascular-Disrupting Agent Combretastatin A4 Phosphate in Mice","volume":"121","author":"Welford","year":"2011","journal-title":"J. Clin. Investig."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/j.mam.2011.04.005","article-title":"Macrophage Regulation of Tumor Angiogenesis: Implications for Cancer Therapy","volume":"32","author":"Squadrito","year":"2011","journal-title":"Mol. Aspects Med."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"434","DOI":"10.1158\/2159-8290.CD-11-0171","article-title":"Reversing Resistance to Vascular-Disrupting Agents by Blocking Late Mobilization of Circulating Endothelial Progenitor Cells","volume":"2","author":"Taylor","year":"2012","journal-title":"Cancer Discov."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"11520","DOI":"10.1158\/0008-5472.CAN-06-2848","article-title":"Pathophysiologic Effects of Vascular-Targeting Agents and the Implications for Combination with Conventional Therapies","volume":"66","author":"Horsman","year":"2006","journal-title":"Cancer Res."},{"key":"ref_119","doi-asserted-by":"crossref","unstructured":"Drzyzga, A., Cicho\u0144, T., Czapla, J., Jarosz-Biej, M., Pilny, E., Matuszczak, S., Wojcieszek, P., Urba\u015b, Z., and Smolarczyk, R. (2021). The Proper Administration Sequence of Radiotherapy and Anti-Vascular Agent\u2014DMXAA Is Essential to Inhibit the Growth of Melanoma Tumors. Cancers, 13.","DOI":"10.3390\/cancers13163924"},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1016\/j.critrevonc.2012.10.002","article-title":"Combination of Vascular Disrupting Agents and Ionizing Radiation","volume":"86","author":"Chargari","year":"2013","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"ref_121","first-page":"4716","article-title":"Eradication of Colorectal Xenografts by Combined Radioimmunotherapy and Combretastatin A-4 3-O-Phosphate","volume":"61","author":"Pedley","year":"2001","journal-title":"Cancer Res."},{"key":"ref_122","doi-asserted-by":"crossref","first-page":"4484","DOI":"10.1158\/1078-0432.CCR-09-0035","article-title":"A Phase I Trial of Radioimmunotherapy with 131I-A5B7 Anti-CEA Antibody in Combination with Combretastatin-A4-Phosphate in Advanced Gastrointestinal Carcinomas","volume":"15","author":"Meyer","year":"2009","journal-title":"Clin. Cancer Res."},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"792","DOI":"10.2967\/jnumed.110.086116","article-title":"Small-Animal PET of Tumor Damage Induced by Photothermal Ablation with64 Cu-Bis-DOTA-Hypericin","volume":"52","author":"Song","year":"2011","journal-title":"J. Nucl. Med."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"14247","DOI":"10.18632\/oncotarget.3679","article-title":"Necrosis Targeted Radiotherapy with Iodine-131-Labeled Hypericin to Improve Anticancer Efficacy of Vascular Disrupting Treatment in Rabbit VX2 Tumor Models","volume":"6","author":"Shao","year":"2015","journal-title":"Oncotarget"},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.1021\/acs.nanolett.1c00168","article-title":"Platelet-Membrane-Coated Nanoparticles Enable Vascular Disrupting Agent Combining Anti-Angiogenic Drug for Improved Tumor Vessel Impairment","volume":"21","author":"Li","year":"2021","journal-title":"Nano Lett."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1517\/13543784.2013.759557","article-title":"Vascular-Disrupting Agents in Oncology","volume":"22","author":"Mita","year":"2013","journal-title":"Expert Opin. Investig. Drugs"},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"3428","DOI":"10.1158\/1078-0432.CCR-11-3376","article-title":"Phase I Trial of Combretastatin A4 Phosphate (CA4P) in Combination with Bevacizumab in Patients with Advanced Cancer","volume":"18","author":"Nathan","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.ygyno.2020.01.005","article-title":"Pazopanib and Fosbretabulin in Recurrent Ovarian Cancer (PAZOFOS): A Multi-Centre, Phase 1b and Open-Label, Randomised Phase 2 Trial","volume":"156","author":"Morgan","year":"2020","journal-title":"Gynecol. Oncol."},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"107932","DOI":"10.1016\/j.lungcan.2024.107932","article-title":"Phase I\/II Trial of Plinabulin in Combination with Nivolumab and Ipilimumab in Patients with Recurrent Small Cell Lung Cancer (SCLC): Big Ten Cancer Research Consortium (BTCRC-LUN17-127) Study","volume":"195","author":"Malhotra","year":"2024","journal-title":"Lung Cancer"},{"key":"ref_130","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1016\/S2213-2600(24)00178-4","article-title":"Plinabulin plus Docetaxel versus Docetaxel in Patients with Non-Small-Cell Lung Cancer after Disease Progression on Platinum-Based Regimen (DUBLIN-3): A Phase 3, International, Multicentre, Single-Blind, Parallel Group, Randomised Controlled Trial","volume":"12","author":"Han","year":"2024","journal-title":"Lancet Respir. Med."},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"1844","DOI":"10.1038\/sj.bjc.6600992","article-title":"Clinical Aspects of a Phase I Trial of 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA), a Novel Antivascular Agent","volume":"88","author":"Jameson","year":"2003","journal-title":"Br. J. Cancer"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"2553","DOI":"10.1167\/iovs.08-2068","article-title":"Transient Retinal Effects of 5,6-Dimethylxanthenone-4-Acetic Acid (DMXAA, ASA404), an Antitumor Vascular-Disrupting Agent in Phase I Clinical Trials","volume":"50","author":"Jameson","year":"2009","journal-title":"Investig. Opthalmology Vis. Sci."},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"2965","DOI":"10.1200\/JCO.2011.35.0660","article-title":"Randomized Phase III Placebo-Controlled Trial of Carboplatin and Paclitaxel With or Without the Vascular Disrupting Agent Vadimezan (ASA404) in Advanced Non\u2013Small-Cell Lung Cancer","volume":"29","author":"Lara","year":"2011","journal-title":"J. Clin. Oncol."},{"key":"ref_134","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.lungcan.2014.05.013","article-title":"DISRUPT: A Randomised Phase 2 Trial of Ombrabulin (AVE8062) plus a Taxane\u2013Platinum Regimen as First-Line Therapy for Metastatic Non-Small Cell Lung Cancer","volume":"85","author":"Gorbounova","year":"2014","journal-title":"Lung Cancer"},{"key":"ref_135","doi-asserted-by":"crossref","first-page":"586","DOI":"10.1136\/ijgc-2022-003880","article-title":"Phase I Study of Ombrabulin in Combination with Paclitaxel and Carboplatin in Japanese Patients with Advanced Solid Tumors","volume":"34","author":"Matsumoto","year":"2024","journal-title":"Int. J. Gynecol. Cancer"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"2170","DOI":"10.1038\/bjc.2014.137","article-title":"A Phase I Pharmacokinetic Study of the Vascular Disrupting Agent Ombrabulin (AVE8062) and Docetaxel in Advanced Solid Tumours","volume":"110","author":"Eskens","year":"2014","journal-title":"Br. J. Cancer"},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"5152","DOI":"10.1158\/1078-0432.CCR-11-0937","article-title":"Clinical, Pharmacodynamic, and Pharmacokinetic Evaluation of BNC105P: A Phase I Trial of a Novel Vascular Disrupting Agent and Inhibitor of Cancer Cell Proliferation","volume":"17","author":"Rischin","year":"2011","journal-title":"Clin. Cancer Res."},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"1133-e112","DOI":"10.1634\/theoncologist.2018-0292","article-title":"NGR-hTNF and Doxorubicin as Second-Line Treatment of Patients with Small Cell Lung Cancer","volume":"23","author":"Gregorc","year":"2018","journal-title":"Oncologist"},{"key":"ref_139","doi-asserted-by":"crossref","unstructured":"Valentinis, B., Porcellini, S., Asperti, C., Cota, M., Zhou, D., Di Matteo, P., Garau, G., Zucchelli, C., Avanzi, N.R., and Rizzardi, G.P. (2019). Mechanism of Action of the Tumor Vessel Targeting Agent NGR-hTNF: Role of Both NGR Peptide and hTNF in Cell Binding and Signaling. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20184511"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10085\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,21]],"date-time":"2025-10-21T04:15:28Z","timestamp":1761020128000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/20\/10085"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,10,16]]},"references-count":139,"journal-issue":{"issue":"20","published-online":{"date-parts":[[2025,10]]}},"alternative-id":["ijms262010085"],"URL":"https:\/\/doi.org\/10.3390\/ijms262010085","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,10,16]]}}}