Angiogenesis inhibitors as therapeutic agents in cancer: Challenges and future directions

European Journal of Pharmacology

Volumn 793, Issue , 2016, Pages 76-81

  Lin, Zhexuan ^a   Zhang, Quanwei ^a   Luo, Wenhong ^a  

^a SHANTOU UNIVERSITY MEDICAL COLLEGE   (China)

Author keywords

Angiogenesis inhibitors; Cancer therapy; Vascular normalization; Vascular promotion

Indexed keywords

ANGIOGENESIS INHIBITOR; ANTINEOPLASTIC AGENT; PEPTIDE INHIBITOR; PROTEIN INHIBITOR; SMALL MOLECULE INHIBITOR; UNCLASSIFIED DRUG; VASCULAR TARGETING AGENT;

ANTIANGIOGENIC ACTIVITY; CLINICAL EFFECTIVENESS; DRUG APPROVAL; DRUG EFFICACY; DRUG MECHANISM; DRUG RESPONSE; HUMAN; MALIGNANT NEOPLASTIC DISEASE; OUTCOME ASSESSMENT; PRIORITY JOURNAL; REVIEW; ANIMAL; BLOOD VESSEL; DRUG EFFECTS; NEOPLASMS; PATHOPHYSIOLOGY; VASCULARIZATION;

ANGIOGENESIS INHIBITORS; ANIMALS; ANTINEOPLASTIC AGENTS; BLOOD VESSELS; HUMANS; NEOPLASMS;

EID: 85000500151     PISSN: 00142999     EISSN: 18790712     Source Type: Journal    
DOI: 10.1016/j.ejphar.2016.10.039     Document Type: Review

References (80)

1. Al-Rawi, S., Meehan-Andrews, T., Bradley, C., Al-Rawi, J., Novel benzoxazines as inhibitors of angiogenesis. Investig. New Drugs 33 (2015), 45–52.
2. Babae, N., Bourajjaj, M., Liu, Y., Van Beijnum, J.R., Cerisoli, F., Scaria, P.V., Verheul, M., Van Berkel, M.P., Pieters, E.H., Van Haastert, R.J., Yousefi, A., Mastrobattista, E., Storm, G., Berezikov, E., Cuppen, E., Woodle, M., Schaapveld, R.Q., Prevost, G.P., Griffioen, A.W., Van Noort, P.I., Schiffelers, R.M., Systemic miRNA-7 delivery inhibits tumor angiogenesis and growth in murine xenograft glioblastoma. Oncotarget 5 (2014), 6687–6700.
3. Besse, B., Tsao, L.C., Chao, D.T., Fang, Y., Soria, J.C., Almokadem, S., Belani, C.P., Phase Ib safety and pharmacokinetic study of volociximab, an anti-alpha5beta1 integrin antibody, in combination with carboplatin and paclitaxel in advanced non-small-cell lung cancer. Ann. Oncol.: Off. J. Eur. Soc. Med. Oncol./ESMO 24 (2013), 90–96.
4. Blaschuk, O.W., Discovery and development of N-cadherin antagonists. Cell Tissue Res. 348 (2012), 309–313.
5. Bokemeyer, C., Van Cutsem, E., Rougier, P., Ciardiello, F., Heeger, S., Schlichting, M., Celik, I., Kohne, C.H., Addition of cetuximab to chemotherapy as first-line treatment for KRAS wild-type metastatic colorectal cancer: pooled analysis of the CRYSTAL and OPUS randomised clinical trials. Eur. J. Cancer 48 (2012), 1466–1475.
6. Bold, G., Schnell, C., Furet, P., McSheehy, P., Bruggen, J., Mestan, J., Manley, P.W., Druckes, P., Burglin, M., Durler, U., Loretan, J., Reuter, R., Wartmann, M., Theuer, A., Bauer-Probst, B., Martiny-Baron, G., Allegrini, P., Goepfert, A., Wood, J., Littlewood-Evans, A., A Novel Potent Oral Series of VEGFR2 Inhibitors Abrogate Tumor Growth by Inhibiting Angiogenesis. J. Med. Chem. 59 (2016), 132–146.
7. Brufsky, A.M., Hurvitz, S., Perez, E., Swamy, R., Valero, V., O'Neill, V., Rugo, H.S., RIBBON-2: a randomized, double-blind, placebo-controlled, phase III trial evaluating the efficacy and safety of bevacizumab in combination with chemotherapy for second-line treatment of human epidermal growth factor receptor 2-negative metastatic breast cancer. J. Clin. Oncol.: Off. J. Am. Soc. Clin. Oncol. 29 (2011), 4286–4293.
8. Carmeliet, P., Angiogenesis in life, disease and medicine. Nature 438 (2005), 932–936.
9. Carmeliet, P., Jain, R.K., Principles and mechanisms of vessel normalization for cancer and other angiogenic diseases. Nat. Rev. Drug Discov. 10 (2011), 417–427.
10. Cascone, T., Herynk, M.H., Xu, L., Du, Z., Kadara, H., Nilsson, M.B., Oborn, C.J., Park, Y.Y., Erez, B., Jacoby, J.J., Lee, J.S., Lin, H.Y., Ciardiello, F., Herbst, R.S., Langley, R.R., Heymach, J.V., Upregulated stromal EGFR and vascular remodeling in mouse xenograft models of angiogenesis inhibitor-resistant human lung adenocarcinoma. J. Clin. Investig. 121 (2011), 1313–1328.
11. Castellano, D., del Muro, X.G., Perez-Gracia, J.L., Gonzalez-Larriba, J.L., Abrio, M.V., Ruiz, M.A., Pardo, A., Guzman, C., Cerezo, S.D., Grande, E., Patient-reported outcomes in a phase III, randomized study of sunitinib versus interferon-{alpha} as first-line systemic therapy for patients with metastatic renal cell carcinoma in a European population. Ann. Oncol.: Off. J. Eur. Soc. Med. Oncol. / ESMO 20 (2009), 1803–1812.
12. Dormond, O., Ruegg, C., Regulation of endothelial cell integrin function and angiogenesis by COX-2, cAMP and Protein Kinase A. Thromb. Haemost. 90 (2003), 577–585.
13. Dragovich, T., Laheru, D., Dayyani, F., Bolejack, V., Smith, L., Seng, J., Burris, H., Rosen, P., Hidalgo, M., Ritch, P., Baker, A.F., Raghunand, N., Crowley, J., Von Hoff, D.D., Phase II trial of vatalanib in patients with advanced or metastatic pancreatic adenocarcinoma after first-line gemcitabine therapy (PCRT O4-001). Cancer Chemother. Pharmacol. 74 (2014), 379–387.
14. Ebrahimizadeh, W., Mousavi Gargari, S.L., Javidan, Z., Rajabibazl, M., Production of novel VHH nanobody inhibiting angiogenesis by targeting binding site of VEGF. Appl. Biochem. Biotechnol. 176 (2015), 1985–1995.
15. Ehlers, T., Furness, S., Robinson, T.P., Zhong, H.A., Goldsmith, D., Aribser, J., Bowen, J.P., Methionine AminoPeptidase Type-2 inhibitors targeting angiogenesis. Curr. Top. Med. Chem. 16 (2016), 1478–1488.
16. El-Kenawi, A.E., El-Remessy, A.B., Angiogenesis inhibitors in cancer therapy: mechanistic perspective on classification and treatment rationales. Br. J. Pharmacol. 170 (2013), 712–729.
17. Erler, J.T., Bennewith, K.L., Cox, T.R., Lang, G., Bird, D., Koong, A., Le, Q.T., Giaccia, A.J., Hypoxia-induced lysyl oxidase is a critical mediator of bone marrow cell recruitment to form the premetastatic niche. Cancer Cell 15 (2009), 35–44.
18. Escudier, B., Eisen, T., Stadler, W.M., Szczylik, C., Oudard, S., Staehler, M., Negrier, S., Chevreau, C., Desai, A.A., Rolland, F., Demkow, T., Hutson, T.E., Gore, M., Anderson, S., Hofilena, G., Shan, M., Pena, C., Lathia, C., Bukowski, R.M., Sorafenib for treatment of renal cell carcinoma: final efficacy and safety results of the phase III treatment approaches in renal cancer global evaluation trial. J. Clin. Oncol.: Off. J. Am. Soc. Clin. Oncol. 27 (2009), 3312–3318.
19. Ferrara, N., Gerber, H.P., LeCouter, J., The biology of VEGF and its receptors. Nat. Med. 9 (2003), 669–676.
20. Ferrara, N., Hillan, K.J., Gerber, H.P., Novotny, W., Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer. Nat. Rev. Drug Discov. 3 (2004), 391–400.
21. Folkman, J., Anti-angiogenesis: new concept for therapy of solid tumors. Ann. Surg. 175 (1972), 409–416.
22. Franks, M.E., Macpherson, G.R., Figg, W.D., Thalidomide. Lancet 363 (2004), 1802–1811.
23. Gahr, S., Wissniowski, T., Zopf, S., Strobel, D., Pustowka, A., Ocker, M., Combination of the deacetylase inhibitor panobinostat and the multi-kinase inhibitor sorafenib for the treatment of metastatic hepatocellular carcinoma - review of the underlying molecular mechanisms and first case report. J. Cancer 3 (2012), 158–165.
24. Gahr, S., Mayr, C., Kiesslich, T., Illig, R., Neureiter, D., Alinger, B., Ganslmayer, M., Wissniowski, T., Fazio, P.D., Montalbano, R., Ficker, J.H., Ocker, M., Quint, K., The pan-deacetylase inhibitor panobinostat affects angiogenesis in hepatocellular carcinoma models via modulation of CTGF expression. Int. J. Oncol. 47 (2015), 963–970.
25. Gan, H.K., Seruga, B., Knox, J.J., Sunitinib in solid tumors. Expert Opin. Investig. Drugs 18 (2009), 821–834.
26. Grabowski, J., Glode, A., Ramucirumab: a vascular endothelial growth factor receptor-2 inhibitor with activity in several malignancies. Am. J. Health-Syst. Pharm.: AJHP: Off. J. Am. Soc. Health-Syst. Pharm. 73 (2016), 957–968.
27. Haas, N.B., Manola, J., Uzzo, R.G., Flaherty, K.T., Wood, C.G., Kane, C., Jewett, M., Dutcher, J.P., Atkins, M.B., Pins, M., Wilding, G., Cella, D., Wagner, L., Matin, S., Kuzel, T.M., Sexton, W.J., Wong, Y.N., Choueiri, T.K., Pili, R., Puzanov, I., Kohli, M., Stadler, W., Carducci, M., Coomes, R., DiPaola, R.S., Adjuvant sunitinib or sorafenib for high-risk, non-metastatic renal-cell carcinoma (ECOG-ACRIN E2805): a double-blind, placebo-controlled, randomised, phase 3 trial. Lancet 387 (2016), 2008–2016.
28. Hanahan, D., Folkman, J., Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86 (1996), 353–364.
29. Hanahan, D., Weinberg, R.A., Hallmarks of cancer: the next generation. Cell 144 (2011), 646–674.
30. Hinnen, P., Eskens, F.A., vascular disrupting agents in Clinical development. Br. J. Cancer 96 (2007), 1159–1165.
31. Ho, T.H., Jonasch, E., Axitinib in the treatment of metastatic renal cell carcinoma. Future Oncol. 7 (2011), 1247–1253.
32. Hong, S., Tan, M., Wang, S., Luo, S., Chen, Y., Zhang, L., Efficacy and safety of angiogenesis inhibitors in advanced non-small cell lung cancer: a systematic review and meta-analysis. J. Cancer Res. Clin. Oncol. 141 (2015), 909–921.
33. Hsu, J.Y., Wakelee, H.A., Monoclonal antibodies targeting vascular endothelial growth factor: current status and future challenges in cancer therapy. BioDrugs: Clin. Immunother., Biopharm. gene Ther. 23 (2009), 289–304.
34. Huang, D., Ding, Y., Li, Y., Luo, W.M., Zhang, Z.F., Snider, J., VandenBeldt, K., Qian, C.N., Teh, B.T., Sunitinib acts primarily on tumor endothelium rather than tumor cells to inhibit the growth of renal cell carcinoma. Cancer Res. 70 (2010), 1053–1062.
35. Hurwitz, H., Fehrenbacher, L., Novotny, W., Cartwright, T., Hainsworth, J., Heim, W., Berlin, J., Baron, A., Griffing, S., Holmgren, E., Ferrara, N., Fyfe, G., Rogers, B., Ross, R., Kabbinavar, F., Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. New Engl. J. Med. 350 (2004), 2335–2342.
36. Karagiannis, E.D., Popel, A.S., Novel anti-angiogenic peptides derived from ELR-containing CXC chemokines. J. Cell. Biochem. 104 (2008), 1356–1363.
37. Keck, P.J., Hauser, S.D., Krivi, G., Sanzo, K., Warren, T., Feder, J., Connolly, D.T., Vascular permeability factor, an endothelial cell mitogen related to PDGF. Science 246 (1989), 1309–1312.
38. Kim, J.H., Park, I., Lee, J.L., Pazopanib versus sunitinib for the treatment of metastatic renal cell carcinoma patients with poor-risk features. Cancer Chemother. Pharmacol. 78 (2016), 325–332.
39. Kim, K.J., Li, B., Winer, J., Armanini, M., Gillett, N., Phillips, H.S., Ferrara, N., Inhibition of vascular endothelial growth factor-induced angiogenesis suppresses tumour growth in vivo. Nature 362 (1993), 841–844.
40. Kirk, N.S., Bezos, A., Willis, A.C., Sudta, P., Suksamrarn, S., Parish, C.R., Ranson, M., Kelso, M.J., Synthesis and preliminary evaluation of 5,7-dimethyl-2-aryl-3H-pyrrolizin-3-ones as angiogenesis inhibitors. Bioorg. Med. Chem. Lett. 26 (2016), 1813–1816.
41. Lai, L., Liu, J.C., Zhai, D., Lin, Q.X., He, L.J., Dong, Y.M., Zhang, J., Lu, B.B., Chen, Y.H., Yi, Z.F., Liu, M.Y., Plumbagin inhibits tumour angiogenesis and tumour growth through the Ras signalling pathway following activation of the VEGF receptor-2. Brit J. Pharm. 165 (2012), 1084–1096.
42. Lamdan, H., Ayala, M., Rojas, G., Munoz, Y., Morera, Y., Guirola, O., Chinea, G., Gavilondo, J.V., Isolation of a novel neutralizing antibody fragment against human vascular endothelial growth factor from a phage-displayed human antibody repertoire using an epitope disturbing strategy. J. Biotechnol. 151 (2011), 166–174.
43. Langmuir, P.B., Yver, A., Vandetanib for the treatment of thyroid cancer. Clin. Pharmacol. Ther. 91 (2012), 71–80.
44. Le Tourneau, C., Raymond, E., Faivre, S., Sunitinib: a novel tyrosine kinase inhibitor. A brief review of its therapeutic potential in the treatment of renal carcinoma and gastrointestinal stromal tumors (GIST). Ther. Clin. risk Manag. 3 (2007), 341–348.
45. Li, X.Y., Zhu, S.J., Hong, C.Q., Cai, H.Q., Angiogenesis inhibitors for patients with ovarian cancer: a meta-analysis of 12 randomized controlled trials. Curr. Med Res Opin. 32 (2016), 555–562.
46. Lorusso, P.M., Boerner, S.A., Hunsberger, S., Clinical development of vascular disrupting agents: what lessons can we learn from ASA404?. J. Clin. Oncol.: Off. J. Am. Soc. Clin. Oncol. 29 (2011), 2952–2955.
47. Lu, Y., Yang, J., Sega, E., Issues related to targeted delivery of proteins and peptides. AAPS J. 8 (2006), E466–E478.
48. Miller, K., Wang, M., Gralow, J., Dickler, M., Cobleigh, M., Perez, E.A., Shenkier, T., Cella, D., Davidson, N.E., Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. New Engl. J. Med. 357 (2007), 2666–2676.
49. Muthukumarasamy, K.M., Handore, K.L., Kakade, D.N., Shinde, M.V., Ranjan, S., Kumar, N., Sehrawat, S., Sachidanandan, C., Reddy, D.S., Identification of noreremophilane-based inhibitors of angiogenesis using zebrafish assays. Org. Biomol. Chem. 14 (2016), 1569–1578.
50. Nakamura, T., Matsumoto, K., Angiogenesis inhibitors: from laboratory to clinical application. Biochem. Biophys. Res. Commun. 333 (2005), 289–291.
51. Paez-Ribes, M., Allen, E., Hudock, J., Takeda, T., Okuyama, H., Vinals, F., Inoue, M., Bergers, G., Hanahan, D., Casanovas, O., Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15 (2009), 220–231.
52. Popat, S., Mellemgaard, A., Fahrbach, K., Martin, A., Rizzo, M., Kaiser, R., Griebsch, I., Reck, M., Nintedanib plus docetaxel as second-line therapy in patients with non-small-cell lung cancer: a network meta-analysis. Future Oncol. 11 (2015), 409–420.
53. Pugh, C.W., Ratcliffe, P.J., Regulation of angiogenesis by hypoxia: role of the HIF system. Nat. Med. 9 (2003), 677–684.
54. Raddum, A.M., Evensen, L., Hollas, H., Grindheim, A.K., Lorens, J.B., Vedeler, A., Domains I and IV of annexin A2 affect the formation and integrity of in vitro capillary-like networks. PloS One, 8, 2013, e60281.
55. Raddum, A.M., Hollas, H., Shumilin, I.A., Henklein, P., Kretsinger, R., Fossen, T., Vedeler, A., The native structure of annexin A2 peptides in hydrophilic environment determines their anti-angiogenic effects. Biochem. Pharmacol. 95 (2015), 1–15.
56. Redlitz, A., Daum, G., Sage, E.H., Angiostatin diminishes activation of the mitogen-activated protein kinases ERK-1 and ERK-2 in human dermal microvascular endothelial cells. J. Vasc. Res. 36 (1999), 28–34.
57. Rosca, E.V., Koskimaki, J.E., Rivera, C.G., Pandey, N.B., Tamiz, A.P., Popel, A.S., Anti-angiogenic peptides for cancer therapeutics. Curr. Pharm. Biotechnol. 12 (2011), 1101–1116.
58. Scartozzi, M., Vincent, L., Chiron, M., Cascinu, S., Aflibercept, a new way to target angiogenesis in the second line treatment of metastatic colorectal cancer (mCRC). Target. Oncol. 11 (2016), 489–500.
59. Schwartz, J.D., Rowinsky, E.K., Youssoufian, H., Pytowski, B., Wu, Y., Vascular endothelial growth factor receptor-1 in human cancer: concise review and rationale for development of IMC-18F1 (human antibody targeting Vascular endothelial growth factor receptor-1). Cancer 116 (2010), 1027–1032.
60. Semenza, G.L., Oxygen sensing, hypoxia-inducible factors, and disease pathophysiology. Annu. Rev. Pathol. 9 (2014), 47–71.
61. Sharma, M.C., Sharma, M., The role of annexin II in angiogenesis and tumor progression: a potential therapeutic target. Curr. Pharm. Des. 13 (2007), 3568–3575.
62. Shojaei, F., Wu, X., Qu, X., Kowanetz, M., Yu, L., Tan, M., Meng, Y.G., Ferrara, N., G-CSF-initiated myeloid cell mobilization and angiogenesis mediate tumor refractoriness to anti-VEGF therapy in mouse models. Proc. Natl. Acad. Sci. USA 106 (2009), 6742–6747.
63. Singh, S.R., Rameshwar, P., Siegel, P., 2016. Targeting tumor microenvironment in cancer therapy. Cancer letters.
64. Sleijfer, S., Ray-Coquard, I., Papai, Z., Le Cesne, A., Scurr, M., Schoffski, P., Collin, F., Pandite, L., Marreaud, S., De Brauwer, A., van Glabbeke, M., Verweij, J., Blay, J.Y., Pazopanib, a multikinase angiogenesis inhibitor, in patients with relapsed or refractory advanced soft tissue sarcoma: a phase II study from the European organisation for research and treatment of cancer-soft tissue and bone sarcoma group (EORTC study 62043). J. Clin. Oncol.: Off. J. Am. Soc. Clin. Oncol. 27 (2009), 3126–3132.
65. Sotelo, M.J., Garcia-Paredes, B., Aguado, C., Sastre, J., Diaz-Rubio, E., Role of cetuximab in first-line treatment of metastatic colorectal cancer. World J. Gastroenterol. 20 (2014), 4208–4219.
66. Staton, C.A., Brown, N.J., Reed, M.W., Current status and future prospects for anti-angiogenic therapies in cancer. Expert Opin. Drug Discov. 4 (2009), 961–979.
67. Strawn, L.M., McMahon, G., App, H., Schreck, R., Kuchler, W.R., Longhi, M.P., Hui, T.H., Tang, C., Levitzki, A., Gazit, A., Chen, I., Keri, G., Orfi, L., Risau, W., Flamme, I., Ullrich, A., Hirth, K.P., Shawver, L.K., Flk-1 as a target for tumor growth inhibition. Cancer Res. 56 (1996), 3540–3545.
68. Tang, H., Ma, H., Peng, F., Bao, Y., Hu, X., Wang, J., Xu, Y., Chen, M., Prognostic performance of inflammation-based Prognostic indices in locally advanced non-small-lung cancer treated with endostar and concurrent chemoradiotherapy. Mol. Clin. Oncol. 4 (2016), 801–806.
69. Tewari, K.S., Sill, M.W., Long, H.J. 3rd, Penson, R.T., Huang, H., Ramondetta, L.M., Landrum, L.M., Oaknin, A., Reid, T.J., Leitao, M.M., Michael, H.E., Monk, B.J., Improved survival with bevacizumab in advanced cervical cancer. New Engl. J. Med. 370 (2014), 734–743.
70. Thornton, K., Kim, G., Maher, V.E., Chattopadhyay, S., Tang, S., Moon, Y.J., Song, P., Marathe, A., Balakrishnan, S., Zhu, H., Garnett, C., Liu, Q., Booth, B., Gehrke, B., Dorsam, R., Verbois, L., Ghosh, D., Wilson, W., Duan, J., Sarker, H., Miksinski, S.P., Skarupa, L., Ibrahim, A., Justice, R., Murgo, A., Pazdur, R., Vandetanib for the treatment of symptomatic or progressive medullary thyroid cancer in patients with unresectable locally advanced or metastatic disease: U.S. Food and Drug Administration drug approval summary. Clin. Cancer Res.: Off. J. Am. Assoc. Cancer Res. 18 (2012), 3722–3730.
71. Tolsma, S.S., Volpert, O.V., Good, D.J., Frazier, W.A., Polverini, P.J., Bouck, N., Peptides derived from two separate domains of the matrix protein thrombospondin-1 have anti-angiogenic activity. J. Cell Biol. 122 (1993), 497–511.
72. Torre, L.A., Siegel, R.L., Ward, E.M., Jemal, A., 2016. Global Cancer Incidence and Mortality Rates and Trends-An Update. Cancer epidemiology, biomarkers & prevention: a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 25, 16–27.
73. von Tell, D., Armulik, A., Betsholtz, C., Pericytes and vascular stability. Exp. Cell Res. 312 (2006), 623–629.
74. Wang, H., Man, L., Li, G., Huang, G., Wang, J., Comparative efficacy and safety of axitinib versus sorafenib in metastatic renal cell carcinoma: a systematic review and meta-analysis. OncoTargets Ther. 9 (2016), 3423–3432.
75. Wang, P., Luo, Y., Duan, H., Xing, S., Zhang, J., Lu, D., Feng, J., Yang, D., Song, L., Yan, X., MicroRNA 329 suppresses angiogenesis by targeting CD146. Mol. Cell. Biol. 33 (2013), 3689–3699.
76. Wang, Y.Q., Miao, Z.H., Marine-derived angiogenesis inhibitors for cancer therapy. Mar. Drugs 11 (2013), 903–933.
77. Wong, P.P., Demircioglu, F., Ghazaly, E., Alrawashdeh, W., Stratford, M.R., Scudamore, C.L., Cereser, B., Crnogorac-Jurcevic, T., McDonald, S., Elia, G., Hagemann, T., Kocher, H.M., Hodivala-Dilke, K.M., Dual-action combination therapy enhances angiogenesis while reducing tumor growth and spread. Cancer Cell 27 (2015), 123–137.
78. Yarom, N., Stewart, D., Malik, R., Wells, J., Avruch, L., Jonker, D.J., Phase I clinical trial of Exherin (ADH-1) in patients with advanced solid tumors. Curr. Clin. Pharmacol. 8 (2013), 81–88.
79. Zalcman, G., Mazieres, J., Margery, J., Greillier, L., Audigier-Valette, C., Moro-Sibilot, D., Molinier, O., Corre, R., Monnet, I., Gounant, V., Riviere, F., Janicot, H., Gervais, R., Locher, C., Milleron, B., Tran, Q., Lebitasy, M.P., Morin, F., Creveuil, C., Parienti, J.J., Scherpereel, A., Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): a randomised, controlled, open-label, phase 3 trial. Lancet 387 (2016), 1405–1414.
80. Zhang, Q., Lin, Z., Yin, X., Tang, L., Luo, H., Li, H., Zhang, Y., Luo, W., In vitro and in vivo study of hydralazine, a potential anti-angiogenic agent. Eur. J. Pharmacol. 779 (2016), 138–146.