Targeting Tumor Angiogenesis

Chapter
First Online:

Abstract

Four decades after the seminal work of Judah Folkman, in 1971, cancer therapies based on the suppression of neo-angiogenesis (Folkman, N Engl J Med 285:1182–1186, 1971) are becoming a reality (Verheul et al., Clin Cancer Res 14(11):3589–3597, 2008).

The shift toward the up-regulation of pro-angiogenic factors secretion from both tumor and stroma, results from the interplay between endothelial cell activation, proliferation, extracellular matrix degradation, migration, canalization. It leads to the generation of a chaotic vascular vessels network in prostate cancer tissue (Ahmed and Bicknell, Method Mol Biol 467:3–24, 2009), which can be detected also by modern imaging techniques based on magnetic resonance, ultrasound, and nuclear imaging through targeting of key angiogenic factors (Russo et al., BJU Int 110(11 Pt C):E794–E808, 2012).

This hopefully will lead to further improvements in prostate cancer diagnosis and staging. Preclinical evidence indicates that angiogenesis inhibitors can improve the efficacy of conventional cytotoxic agents mainly by normalizing tumor blood flow, thus improving drug delivery. Although significant biological activity of most vascular growth factors-interfering agents is demonstrated in preclinical models, single-agent activity is almost universally poor (Aragon-Ching et al., J Oncol 2010:361836, 2010). Due to the redundancy within the signalling pathways that promote angiogenesis, combining anti-angiogenic agents with different mechanisms of action seems likely to significatively potentiate their therapeutic efficacy (Corcoran and Gleave 2012; Ellis and Hicklin, Nat Rev Cancer 8:579–591, 2008; Verheul et al., Cancer Chemother Pharmacol 60:29–39, 2007).

Keywords

Prostate Cancer Antiangiogenic Therapy Prostate Cancer Progression CRPC Patient Metastatic CRPC 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
This is a preview of subscription content, log in to check access.

References

  1. Ahmed Z, Bicknell R (2009) Angiogenic signalling pathways. Methods Mol Biol 467:3–24PubMedCrossRefGoogle Scholar
  2. Airley RE, Monaghan JE, Stratford IJ (2000) Hypoxia and disease: opportunities for novel diagnostic and therapeutic prodrug strategies. Pharm J 264:666–673Google Scholar
  3. An WG, Kanekal M, Simon MC, Maltepe E, Blagosklonny MV, Neckers LM (1998) Stabilization of wild-type p53 by hypoxiainducible factor-1a. Nature 392:405–408PubMedCrossRefGoogle Scholar
  4. Antonarakis ES, Armstrong AJ (2011) Emerging therapeutic approaches in the management of metastatic castration-resistant prostate cancer. Prostate Cancer Prostatic Dis 14(3):206–218PubMedCrossRefGoogle Scholar
  5. Aragon-Ching JB, Dahut WL (2009) VEGF inhibitors and prostate cancer therapy. Curr Mol Pharmacol 2:161–168PubMedGoogle Scholar
  6. Aragon-Ching JB, Madan RA, Dahut WL (2010) Angiogenesis inhibition in prostate cancer: current uses and future promises. J Oncol 2010:361836PubMedCrossRefGoogle Scholar
  7. Botelho F, Pina F, Lunet N (2010) VEGF and prostate cancer: a systematic review. Eur J Cancer Prev 19:385–392PubMedCrossRefGoogle Scholar
  8. Brown JM (1999) The hypoxic cell: a target for selective cancer therapy – eighteenth Bruce F. Cain Memorial Award Lecture. Cancer Res 59:5863–5870PubMedGoogle Scholar
  9. Chi KN, Eisenhauer E, Fazli L et al (2005) A phase I pharmacokinetic and pharmacodynamic study of OGX-011, a 2′-methoxyethyl antisense oligonucleotide to clusterin, in patients with localized prostate cancer. J Natl Cancer Inst 97:1287–1296PubMedCrossRefGoogle Scholar
  10. Chi KN, Hotte SJ, Yu EY et al (2009) Mature results of a randomized phase II study of OGX-011 in combination with docetaxel/prednisone versus docetaxel/prednisone in patients with metastatic castration-resistant prostate cancer [abstract 5012]. J Clin Oncol 27(15 suppl):238sGoogle Scholar
  11. Chung LW, Baseman A, Assikis V, Zhau HE (2005) Molecular insights into prostate cancer progression: the missing link of tumor microenvironment. J Urol 1(73):10–20CrossRefGoogle Scholar
  12. Corcoran NM, Gleave ME (2012) Targeted therapy in prostate cancer. Histopathology 60(1):216–231PubMedCrossRefGoogle Scholar
  13. Cvetkovic D, Movsas B, Dicker AP, Hanlon AL, Greenberg RE, Chapman JD, Hanks GE, Tricoli JV (2001) Increased hypoxia correlates with increased expression of the angiogenesis marker vascular endothelial growth factor in human prostate cancer. Urology 57(4):821–825PubMedCrossRefGoogle Scholar
  14. Dayyani F, Gallick GE, Logothetis CJ, Corn PG (2011) Novel therapies for metastatic castrate-resistant prostate cancer. J Natl Cancer Inst 103(22):1665–1675PubMedCrossRefGoogle Scholar
  15. Deryugina EI, Quigley JP (2006) Matrix metalloproteinases and tumor metastasis. Cancer Metastasis Rev 25:9–34PubMedCrossRefGoogle Scholar
  16. Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: mechanisms of antitumour activity. Nat Rev Cancer 8:579–591PubMedCrossRefGoogle Scholar
  17. Ferrer FA, Miller LJ, Andrawis RI et al (1998) Angiogenesis and prostate cancer: in vivo and in vitro expression of angiogenesis factors by prostate cancer cells. Urology 51:161–167PubMedCrossRefGoogle Scholar
  18. Folkman J (1971) Tumour angiogenesis: therapeutic implications. N Engl J Med 285:1182–1186PubMedCrossRefGoogle Scholar
  19. Forsythe JA, Jiang BH, Iyer NV et al (1996) Activation of vascular endothelial growth factor gene transcription by hypoxia-inducible factor 1. Mol Cell Biol 16:4604–4613PubMedGoogle Scholar
  20. Fregene TA, Khanuja PS, Noto AC et al (1993) Tumor-associated angiogenesis in prostate cancer. Anticancer Res 13:2377–2381PubMedGoogle Scholar
  21. George DJ, Armstrong AJ, Creel P et al (2011) A phase II study of RAD001 in men with hormone-refractory metastatic prostate cancer (HRPC) [abstract 181]. Presented at the 2008 American Society of Clinical Oncology Genitourinary Cancers symposium, San Francisco, 14–16 Feb 2008. Available at: http://www.asco.org/ASCOv2/Meetings/Abstracts. Accessed 8 Feb 2011
  22. Gordon IO, Tretiakova MS, Noffsinger AE, Hart J, Reuter VE, Al-Ahmadie HA (2008) Prostate-specific membrane antigen expression in regeneration and repair. Mod Pathol 12:1421–1427CrossRefGoogle Scholar
  23. Gravdal K, Halvorsen OJ, Haukaas SA, Akslen LA (2009) Proliferation of immature tumor vessels is a novel marker of clinical progression in prostate cancer. Cancer Res 69:4708–4715PubMedCrossRefGoogle Scholar
  24. Gross ME, Soscia J, Sakowsky S et al (2009) Phase I trial of RAD001, bevacizumab, and docetaxel for castration-resistant prostate cancer [abstract 5154]. J Clin Oncol 27(15 suppl):272sGoogle Scholar
  25. Jackson MW, Roberts JS, Heckford SE et al (2002) A potential autocrine role for vascular endothelial growth factor in prostate cancer. Cancer Res 62:854–859PubMedGoogle Scholar
  26. Lee LF, Guan J, Qiu Y, Kung HJ (2001a) Neuropeptide-induced androgen independence in prostate cancer cells: roles of nonreceptor tyrosine kinases Etk/Bmx, Src, and focal adhesion kinase. Mol Cell Biol 21:8385–8397PubMedCrossRefGoogle Scholar
  27. Lee SE, Chung WJ, Kwak HB et al (2001b) Tumor necrosis factor-alpha supports the survival of osteoclasts through the activation of Akt and ERK. J Biol Chem 276:49343–49349PubMedCrossRefGoogle Scholar
  28. Lee LF, Louie MC, Desai SJ et al (2004) Interleukin-8 confers androgenin dependent growth and migration of LNCaP: differential effects of tyrosine kinases Src and FAK. Oncogene 23:2197–2205PubMedCrossRefGoogle Scholar
  29. Merino M, Pinto A, González R, Espinosa E (2011) Antiangiogenic agents and endothelin antagonists in advanced castration resistant prostate cancer. Eur J Cancer 47(12):1846–1851PubMedCrossRefGoogle Scholar
  30. Minchenko A, Bauer T, Salceda S, Caro J (1994) Hypoxic stimulation of vascular endothelial growth factor expression in vitro and in vivo. Lab Invest 71:374–379PubMedGoogle Scholar
  31. Park SI, Shah AN, Zhang J, Gallick GE (2007) Regulation of angiogenesis and vascular permeability by Src family kinases: opportunities for therapeutic treatment of solid tumors. Expert Opin Ther Targets 11:1207–1217PubMedCrossRefGoogle Scholar
  32. Peters KB, Wang H, Brown JM, Iliakis G (2001) Inhibition of DNA replication by Tirapazamine. Cancer Res 61:5425–5431PubMedGoogle Scholar
  33. Pidgeon GP, Barr MP, Harmey JH, Foley DA, Bouchier-Hayes DJ (2001) Vascular endothelial growth factor (VEGF) up regulates Bcl-2 and inhibits apoptosis in human and murine mammary adenocarcinoma cells. Br J Cancer 85:273–278PubMedCrossRefGoogle Scholar
  34. Pili R, Donehower RC (2003) Is HIF-1a a valid therapeutic target? J Natl Cancer Inst 95:498–499PubMedCrossRefGoogle Scholar
  35. Pouyssegur J, Dayan F, Mazure NM (2006) Hypoxia signalling in cancer and approaches to enforce tumour regression. Nature 441:437–443PubMedCrossRefGoogle Scholar
  36. Powles T, Chowdhury S, Jones R et al (2011) Sunitinib and other targeted therapies for renal cell carcinoma. Br J Cancer 104:741–745PubMedCrossRefGoogle Scholar
  37. Qian DZ, Wang X, Kachhap SK et al (2004) The histone deacetylase inhibitor NVP-LAQ824 inhibits angiogenesis and has a greater antitumor effect in combination with the vascular endothelial growth factor receptor tyrosine kinase inhibitor PTK787/ZK222584. Cancer Res 64:6626–6634PubMedCrossRefGoogle Scholar
  38. Qian DZ, Kachhap SK, Collis SJ et al (2006a) Class II histone deacetylases are associated with VHL-independent regulation of hypoxia-inducible factor 1a. Cancer Res 66:8814–8821PubMedCrossRefGoogle Scholar
  39. Qian DZ, Kato Y, Shabbeer S et al (2006b) Targeting tumor angiogenesis with histone deacetylase inhibitors: the hydroxamic acid derivative LBH589. Clin Cancer Res 12:634–642PubMedCrossRefGoogle Scholar
  40. Rang HP, Dall MM, Ritter JM (1999) Pharmacology, 4th edn. Churchill Livingstone, Edinburgh, pp 670–677Google Scholar
  41. Ravi R, Mookerjee B, Bhujwalla ZM et al (2000) Regulation of tumor angiogenesis by p53-induced degradation of hypoxia inducible factor 1alpha. Genes Dev 14:34–44PubMedGoogle Scholar
  42. Russell J, Bennett S, Stricker P (1998) Growth factor involvement in progression of prostate cancer. Clin Chem 44:705–723PubMedGoogle Scholar
  43. Russo G, Mischi M, Scheepens W, De la Rosette JJ, Wijkstra H (2012) Angiogenesis in prostate cancer: onset, progression and imaging. BJU Int 110(11 Pt C):E794–E808PubMedCrossRefGoogle Scholar
  44. Semenza GL (2003) Targeting HIF-1for cancer therapy. Nat Rev Cancer 3:721–732PubMedCrossRefGoogle Scholar
  45. Shannon AM, Bouchier-Hayes DJ, Condron CM, Toomey D (2003) Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev 29(4):297–307, ReviewPubMedCrossRefGoogle Scholar
  46. Shariat SF, Anwuri VA, Lamb DJ, Shah NV, Wheeler TM, Slawin KM (2004) Association of preoperative plasma levels of vascular endothelial growth factor and soluble vascular cell adhesion molecule – 1 with lymph node status and biochemical progression after radical prostatectomy. J Clin Oncol 22:1655–1663PubMedCrossRefGoogle Scholar
  47. Shih SC, Claffey KP (1998) Hypoxia-mediated regulation of gene expression in mammalian cells. Int J Exp Pathol 79:347–357PubMedCrossRefGoogle Scholar
  48. Shweiki D, Itin A, Soffer D, Keshet E (1992) Vascular endothelial growth factor induced by hypoxia may mediate hypoxia initiated angiogenesis. Nature 359:843–845PubMedCrossRefGoogle Scholar
  49. Shweiki D, Neeman M, Itin A, Keshet E (1995) Induction of vascular endothelial growth factor expression by hypoxia and by glucose deficiency in multicell spheroids: implications for tumour angiogenesis. Proc Natl Acad Sci USA 92:768–772PubMedCrossRefGoogle Scholar
  50. Siim BG, van Zijl PL, Brown JM (1996) Tirapazamine-induced DNA damage measured using the comet assay correlates with cytotoxicity towards hypoxic tumour cells in vitro. Br J Cancer 73:952–960PubMedCrossRefGoogle Scholar
  51. Sowery RD, Hadaschik BA, So AI et al (2008) Clusterin knockdown using the antisense oligonucleotide OGX-011 re-sensitizes docetaxel-refractory prostate cancer PC-3 cells to chemotherapy. BJU Int 102:389–397PubMedCrossRefGoogle Scholar
  52. Strohmeyer D, Rossing C, Strauss F, Bauerfeind A, Kaufmann O, Loening S (2000) Tumor angiogenesis is associated with progression after radical prostatectomy in pT2/pT3 prostate cancer. Prostate 42:26–33PubMedCrossRefGoogle Scholar
  53. Sturge J, Caley MP, Waxman J (2011) Bone metastasis in prostate cancer: emerging therapeutic strategies. Nat Rev Clin Oncol 8(6):357–368PubMedGoogle Scholar
  54. Teicher BA, Holden SA, Al-Achi A, Herman TS (1990) Classification of antineoplastic treatments by their differential toxicity toward putative oxygenated and hypoxic tumour subpopulation in vivo in the FSaIIC murine fibrosarcoma. Cancer Res 50:3339–3344PubMedGoogle Scholar
  55. Treins C, Giorgetti-Peraldi S, Murdaca J, Semenza GL, Van Obberghen E (2002) Insulin stimulates hypoxia inducible factor 1 through a phosphatidylinositol 3-kinase/target of rapamycin-dependent signaling pathway. J Biol Chem 277:27975–27981PubMedCrossRefGoogle Scholar
  56. Vaupel P, Kallinowski F, Okunieff P (1989) Blood flow, oxygen and nutrient supply, and metabolic microenvironment of human tumours: a review. Cancer Res 49:6449–6465PubMedGoogle Scholar
  57. Vergis R, Corbishley CM, Norman AR et al (2008) Intrinsic markers of tumour hypoxia and angiogenesis in localised prostate cancer and outcome of radical treatment: a retrospective analysis of two randomised radiotherapy trials and one surgical cohort study. Lancet Oncol 9:342–351PubMedCrossRefGoogle Scholar
  58. Verheul HM, Qian DZ, Carducci MA, Pili R (2007) Sequence-dependent antitumor effects of differentiation agents in combination with cell cycle-dependent cytotoxic drugs. Cancer Chemother Pharmacol 60:29–39CrossRefGoogle Scholar
  59. Verheul HM, Salumbides B, Van Erp K, Hammers H, Qian DZ, Sanni T, Atadja P, Pili R (2008) Combination strategy targeting the hypoxia inducible factor-1 alpha with mammalian target of rapamycin and histone deacetylase inhibitors. Clin Cancer Res 14(11):3589–3597PubMedCrossRefGoogle Scholar
  60. Walker LJ, Craig RB, Harris AL, Hickson ID (1994) A role for the human DNA-repair enzyme HAP1 in cellular-protection against DNA-damaging agents and hypoxic stress. Nucleic Acids Res 22:4884–4889PubMedCrossRefGoogle Scholar
  61. Wang J, Biedermann KA, Brown JM (1992) Repair of DNA and chromosome breaks in cells exposed to SR 4233 under hypoxia or to ionizing radiation. Cancer Res 52:4473–4477PubMedGoogle Scholar
  62. Weidner N, Carroll R, Flax J, Blumenfeld W, Folkman J (1993) Tumor angiogenesis correlates with metastasis in invasive prostate carcinoma. Am J Pathol 143:401–409PubMedGoogle Scholar
  63. Wikström P, Damber J, Bergh A (2001) Role of transforming growth factor-beta1 in prostate cancer. Microsc Res Tech 52:411–419PubMedCrossRefGoogle Scholar
  64. Wu L, Birle DC, Tannock IF (2005) Effects of the mammalian target of rapamycin inhibitor CCI-779 used alone or with chemotherapy on human prostate cancer cells and xenografts. Cancer Res 65:2825–2831PubMedCrossRefGoogle Scholar
  65. Zhong D, Liu X, Khuri FR, Sun SY, Vertino PM, Zhou W (2008) LKB1 is necessary for Akt-mediated phosphorylation of proapoptotic proteins. Cancer Res 68(18):7270–7277PubMedCrossRefGoogle Scholar
  66. Zhu ML, Kyprianou N (2008) Androgen receptor and growth factor signaling cross-talk in prostate cancer cells. Endocr Relat Cancer 15:841–849PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media Dordrecht 2013

Authors and Affiliations

  1. 1.Department of Advanced Biomedical Sciences, Pathology Section, Faculty of Medicine and SurgeryUniversity of Naples “Federico II”NaplesItaly
  2. 2.Unit of Melanoma, Cancer Immunotherapy and Innovative Therapy, Department of MelanomaNational Institute of Tumors Fondazione “G. Pascale”NaplesItaly

Personalised recommendations