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Metastasis: a therapeutic target for cancer

Abstract

Metastasis remains the major driver of mortality in patients with cancer. Our growing body of knowledge regarding this process provides the basis for the development of molecularly targeted therapeutics aimed at the tumor cell or its interaction with the host microenvironment. Here we discuss the similarity and differences between primary tumors and metastases, pathways controlling the colonization of a distant organ, and incorporation of antimetastatic therapies into clinical testing.

Key Points

  • Most information on human cancer is obtained from analysis of primary tumors and yet this knowledge is applied to the treatment of metastases

  • There is mounting genetic evidence that the molecular wiring of a metastatic lesion has both elements in common with and elements that are distinct from those of primary tumors

  • Targeting the last step in the metastatic process, outgrowth at a distant site, termed 'metastatic colonization', holds great therapeutic promise

  • Blockade of metastatic colonization can be accomplished by targeting the metastatic cancer cell or the host cell, or by interrupting reciprocal interactions between tumor cells and the foreign microenvironment; therapeutic efforts can target metastatic colonization at all sites or interactions specific to a particular organ (bone, for instance)

  • Novel clinical trial designs with short-term molecular and pharmacodynamic end points should be considered

  • Approaches to inhibit metastatic colonization may show their best efficacy in the adjuvant setting

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Figure 1: Molecular distinctions between primary colorectal carcinomas and their liver metastases.
Figure 2: Metastatic colonization.
Figure 3: The bone metastasis 'vicious' cycle with recent updates.
Figure 4: An overwhelming number of potential rational combinations of drugs are available for metastatic colonization: angiogenesis as an example.

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References

  1. Steeg PS (2006) Tumor metastasis: mechanistic insights and clinical challenges. Nat Med 12: 895–904

    CAS  PubMed  Google Scholar 

  2. Gupta GP and Massague J (2006) Cancer metastasis: building a framework. Cell 127: 679–695

    CAS  PubMed  Google Scholar 

  3. Hoang CD et al. (2005) Analysis of paired primary lung and lymph node tumor cells: a model of metastatic potential by multiple genetic programs. Cancer Detect Prev 29: 509–517

    CAS  PubMed  Google Scholar 

  4. Roepman P et al. (2006) Maintenance of head and neck tumor gene expression profiles upon lymph node metastasis. Cancer Res 66: 11110–11114

    CAS  PubMed  Google Scholar 

  5. Wang L et al. (2006) Comparison of gene expression profiles between primary tumor and metastatic lesions in gastric cancer patients using laser microdissection and cDNA microarray. World J Gastroenterol 12: 6949–6954

    CAS  PubMed  PubMed Central  Google Scholar 

  6. Yanagawa R et al. (2001) Genome-wide screening of genes showing altered expression in liver metastases of human colorectal cancers by cDNA microarray. Neoplasia 3: 395–401

    CAS  PubMed  PubMed Central  Google Scholar 

  7. Hao X et al. (2004) Differential gene and protein expression in primary breast malignancies and their lymph node metastases as revealed by combined cDNA microarray and tissue microarray analysis. Cancer 100: 1110–1122

    CAS  PubMed  Google Scholar 

  8. Inokuchi M et al. (2004) Gene expression of 5-fluorouracil metabolic enzymes in primary colorectal cancer and corresponding liver metastasis. Cancer Chemother Pharmacol 53: 391–396

    CAS  PubMed  Google Scholar 

  9. Feldmann G et al. (2007) Blockade of hedgehog signaling inhibits pancreatic cancer invasion and metastases: a new paradigm for combination therapy in solid cancers. Cancer Res 67: 2187–2196

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Suzuki M and Tarin D (2007) Gene expression profiling of human lymph node metastases and matched primary breast carcinomas: clinical implications. Mol Oncol 1: 172–180

    PubMed  PubMed Central  Google Scholar 

  11. Diep CB et al. (2006) The order of genetic events associated with colorectal cancer progression inferred from meta-analysis of copy number changes. Genes Chromosomes Cancer 45: 31–41

    CAS  PubMed  Google Scholar 

  12. Albanese I et al. (2004) Heterogeneity within and between primary colorectal carcinomas and matched metastases as revealed by analysis of Ki-ras and p53 mutations. Biochem Biophys Res Commun 325: 784–791

    CAS  PubMed  Google Scholar 

  13. Shah RB et al. (2004) Androgen-independent prostate cancer is a heterogeneous group of diseases: lessons from a rapid autopsy program. Cancer Res 64: 9209–9216

    CAS  PubMed  Google Scholar 

  14. Rinker-Schaeffer CW et al. (2006) Metastasis suppressor proteins: discovery, molecular mechanisms, and clinical application. Clin Cancer Res 12: 3882–3889

    CAS  PubMed  PubMed Central  Google Scholar 

  15. Nash KT et al. (2007) Requirement of KISS1 secretion for multiple organ metastasis suppression and maintenance of tumor dormancy. J Natl Cancer Inst 99: 309–321

    CAS  PubMed  Google Scholar 

  16. Chekmareva M et al. (1998) Chromosome 17-mediated dormancy of AT6.1 prostate cancer micrometastases. Cancer Res 58: 4963–4969

    CAS  PubMed  Google Scholar 

  17. Nagle JA et al. (2004) Involvement of insulin receptor substrate 2 in mammary tumor metastasis. Mol Cell Biol 24: 9726–9735

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Martin SS et al. (2004) A cytoskeleton-based functional genetic screen identifies Bcl-xL as an enhancer of metastasis, but not primary tumor growth. Oncogene 23: 4641–4645

    CAS  PubMed  Google Scholar 

  19. Criscuoli ML et al. (2005) Tumor metastasis but not tumor growth is dependent on Src-mediated vascular permeability. Blood 105: 1508–1514

    CAS  PubMed  Google Scholar 

  20. Witz IP and Levy-Nissenbaum O (2006) The tumor microenvironment in the post-PAGET era. Cancer Lett 242: 1–10

    CAS  PubMed  Google Scholar 

  21. Postovit LM et al. (2006) Influence of the microenvironment on melanoma cell fate determination and phenotype. Cancer Res 66: 7833–7836

    CAS  PubMed  Google Scholar 

  22. Al-Mehdi A et al. (2000) Intravascular origin of metastasis from the proliferation of endothelium-attached tumor cells: a new model for metastasis. Nat Med 6: 100–102

    CAS  PubMed  Google Scholar 

  23. Kaplan RN et al. (2005) VEGFR1-positive haematopoietic bone marrow progenitors initiate the pre-metastatic niche. Nature 438: 820–827

    CAS  PubMed  PubMed Central  Google Scholar 

  24. VanderGriend D et al. (2005) Suppression of metastatic colonization by the context-dependent activation of the c-jun NH2-terminal kinase kinases JNKK1/MKK4 and MKK7. Cancer Res 65: 10984–10991

    CAS  Google Scholar 

  25. Hicklin DJ and Ellis LM (2005) Role of the vascular endothelial growth factor pathway in tumor growth and angiogenesis. J Clin Oncol 23: 1011–1027

    CAS  PubMed  Google Scholar 

  26. Hurwitz H et al. (2004) Bevacizumab plus irinotecan, fluorouracil, and leucovorin for metastatic colorectal cancer. N Engl J Med 350: 2335–2342

    CAS  PubMed  Google Scholar 

  27. Yang JC et al. (2003) A randomized trial of bevacizumab, an anti-vascular endothelial growth factor antibody, for metastatic renal cancer. N Engl J Med 349: 427–434

    CAS  PubMed  PubMed Central  Google Scholar 

  28. Van den Eynden GG et al. (2007) Differential expression of hypoxia and (lymph)angiogenesis-related genes at different metastatic sites in breast cancer. Clin Exp Metastasis 24: 13–23

    CAS  PubMed  Google Scholar 

  29. Casanovas O et al. (2005) Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8: 299–309

    CAS  PubMed  Google Scholar 

  30. Dorrell MI et al. (2007) Combination angiostatic therapy completely inhibits ocular and tumor angiogenesis. Proc Natl Acad Sci USA 104: 967–972

    CAS  PubMed  PubMed Central  Google Scholar 

  31. Wang J et al. (2007) A glycolytic mechanism regulating an angiogenic switch in prostate cancer. Cancer Res 67: 149–159

    CAS  PubMed  Google Scholar 

  32. Stessels F et al. (2004) Breast adenocarcinoma liver metastases, in contrast to colorectal cancer liver metastases, display a non-angiogenic growth pattern that preserves the stroma and lacks hypoxia. Br J Cancer 90: 1429–1436

    CAS  PubMed  PubMed Central  Google Scholar 

  33. Kusters B et al. (2002) Vascular endothelial growth factor-A(165) induces progression of melanoma brain metastases without induction of sprouting angiogenesis. Cancer Res 62: 341–345

    CAS  PubMed  Google Scholar 

  34. Noguera-Troise I et al. (2006) Blockade of Dll4 inhibits tumour growth by promoting non-productive angiogenesis. Nature 444: 1032–1037

    CAS  PubMed  Google Scholar 

  35. Ridgway J et al. (2006) Inhibition of Dll4 signalling inhibits tumour growth by deregulating angiogenesis. Nature 444: 1083–1087

    CAS  PubMed  Google Scholar 

  36. MacKie RM et al. (2003) Fatal melanoma transferred in a donated kidney 16 years after melanoma surgery. N Engl J Med 348: 567–568

    PubMed  Google Scholar 

  37. Naumov G et al. (2002) Persistence of solitary mammary carcinoma cells in a secondary site: a possible contributor to dormancy. Cancer Res 62: 2162–2168

    CAS  PubMed  Google Scholar 

  38. Holmgren L et al. (1995) Dormancy of micrometastases: balanced proliferation and apoptosis in the presence of angiogenesis suppression. Nat Med 1: 149–153

    CAS  PubMed  Google Scholar 

  39. Nierodzik ML and Karpatkin S (2006) Thrombin induces tumor growth, metastasis, and angiogenesis: evidence for a thrombin-regulated dormant tumor phenotype. Cancer Cell 10: 355–362

    CAS  PubMed  Google Scholar 

  40. Dalton W (1999) The tumor microenvironment as a determinant of drug response and resistance. Drug Resist Updat 2: 285–288

    CAS  PubMed  Google Scholar 

  41. Neville-Webbe HL et al. (2004) Osteoprotegerin (OPG) produced by bone marrow stromal cells protects breast cancer cells from TRAIL-induced apoptosis. Breast Cancer Res Treat 86: 269–279

    Google Scholar 

  42. Efstathiou E et al. (2007) Initial modulation of the tumor microenvironment accounts for thalidomide activity in prostate cancer. Clin Cancer Res 13: 1224–1231

    CAS  PubMed  Google Scholar 

  43. Bird NC et al. (2006) Biology of colorectal liver metastases: a review. J Surg Oncol 94: 68–80

    CAS  PubMed  Google Scholar 

  44. Deeken JF and Loscher W (2007) The blood–brain barrier and cancer: transporters, treatment, and trojan horses. Clin Cancer Res 13: 1663–1674

    CAS  PubMed  Google Scholar 

  45. Palmieri D et al. (2007) The biology of metastasis to a sanctuary site. Clin Cancer Res 13: 1656–1662

    CAS  PubMed  Google Scholar 

  46. Roodman G (2004) Mechanisms of bone metastasis. N Engl J Med 350: 1655–1664

    CAS  PubMed  Google Scholar 

  47. Kang Y et al. (2003) A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 3: 537–549

    CAS  PubMed  Google Scholar 

  48. Roudier MP et al. (2003) Phenotypic heterogeneity of end-stage prostate carcinoma metastatic to bone. Hum Pathol 34: 646–653

    PubMed  Google Scholar 

  49. Mundy G (2002) Metastasis to the bone: causes, consequences and therapeutic opportunities. Nat Rev Cancer 2: 584–593

    CAS  PubMed  Google Scholar 

  50. Kishida Y et al. (2007) Parthenolide, a natural inhibitor of nuclear factor-kappaB, inhibits lung colonization of murine osteosarcoma cells. Clin Cancer Res 13: 59–67

    CAS  PubMed  Google Scholar 

  51. Shannon KE et al. (2004) Anti-metastatic properties of RGD-peptidomimetic agents S137 and S247. Clin Exp Metastasis 21: 129–138

    CAS  PubMed  Google Scholar 

  52. Khalili P et al. (2005) Effect of Herceptin on the development and progression of skeletal metastases in a xenograft model of human breast cancer. Oncogene 24: 6657–6666

    CAS  PubMed  Google Scholar 

  53. Slamon D et al. (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344: 783–792

    CAS  PubMed  Google Scholar 

  54. Piccart-Gebhart MJ et al. (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353: 1659–1672

    CAS  PubMed  Google Scholar 

  55. Romond EH et al. (2005) Trastuzumab plus adjuvant chemotherapy for operable HER2-positive breast cancer. N Engl J Med 353: 1673–1684

    CAS  PubMed  Google Scholar 

  56. Tosi P et al. (2006) First-line therapy with thalidomide, dexamethasone and zoledronic acid decreases bone resorption markers in patients with multiple myeloma. Eur J Haematol 76: 399–404

    CAS  PubMed  Google Scholar 

  57. Body J et al. (2002) A phase I study of AMGN-007, a recombinant osterogrotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer 97 (3 Suppl): 887–892

    Google Scholar 

  58. Body JJ et al. (2006) A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 12: 1221–1228

    CAS  PubMed  Google Scholar 

  59. Bochner BH et al. (2006) Postoperative nomogram predicting risk of recurrence after radical cystectomy for bladder cancer. J Clin Oncol 24: 3967–3972

    PubMed  Google Scholar 

  60. Wedam S et al. (2006) Antiangiogenic and antitumor effects of bevacizumab in patients with inflammatory and locally advanced breast cancer. J Clin Oncol 24: 769–777

    CAS  PubMed  Google Scholar 

  61. Jubb AM et al. (2006) Impact of vascular endothelial growth factor-A expression, thrombospondin-2 expression, and microvessel density on the treatment effect of bevacizumab in metastatic colorectal cancer. J Clin Oncol 24: 217–227

    CAS  PubMed  Google Scholar 

  62. Lise M et al. (2005) Colorectal liver metastasis: towards the integration of conventional and molecularly targeted therapeutic approaches. Front Biosci 10: 3042–3057

    CAS  PubMed  Google Scholar 

  63. Herbst RS et al. (2005) Phase I/II trial evaluating the anti-vascular endothelial growth factor monoclonal antibody bevacizumab in combination with the HER-1/epidermal growth factor receptor tyrosine kinase inhibitor erlotinib for patients with recurrent non-small-cell lung cancer. J Clin Oncol 23: 2544–2555

    CAS  PubMed  Google Scholar 

  64. Hainsworth JD et al. (2005) Treatment of metastatic renal cell carcinoma with a combination of bevacizumab and erlotinib. J Clin Oncol 23: 7889–7896

    CAS  PubMed  Google Scholar 

  65. Miller KD et al. (2005) A multicenter phase II trial of ZD6474, a vascular endothelial growth factor receptor-2 and epidermal growth factor receptor tyrosine kinase inhibitor, in patients with previously treated metastatic breast cancer. Clin Cancer Res 11: 3369–3376

    CAS  PubMed  Google Scholar 

  66. Paterson AH (2006) The role of bisphosphonates in early breast cancer. Oncologist 11 (Suppl 1): S13–S19

    Google Scholar 

  67. Diel I et al. (1994) Monoclonal antibodies to detect breast cancer cells in bone marrow. In Important Advances in Oncology, 143–164 (Eds De Vita VT et al.) Philadelphia: Lippincott

    Google Scholar 

  68. Saarto T et al. (2001) Adjuvant clodronate treatment does not reduce the frequency of skeletal metastases in node-positive breast cancer patients; 5-year results of a randomized controlled trial. J Clin Oncol 19: 10–17

    CAS  PubMed  Google Scholar 

  69. Powles T et al. (2002) Randomized, placebo-controlled trial of clodronate in patients with primary operable breast cancer. J Clin Oncol 20: 3219–3224

    CAS  PubMed  Google Scholar 

  70. Saarto T et al. (2004) Ten-year follow-up of a randomized controlled trial of adjuvant clodronate treatment in node-positive breast cancer patients. Acta Oncol 43: 650–656

    CAS  PubMed  Google Scholar 

  71. Bertelli G et al. (2006) Weekly docetaxel and zoledronic acid every 4 weeks in hormone-refractory prostate cancer patients. Cancer Chemother Pharmacol 57: 46–51

    CAS  PubMed  Google Scholar 

  72. Nelson JB et al. (1999) New bone formation in an osteoblastic tumor model is increased by endothelin-1 overexpression and decreased by endothelin A receptor blockade. Urology 53: 1063–1069

    CAS  PubMed  Google Scholar 

  73. Carducci MA and Jimeno A (2006) Targeting bone metastasis in prostate cancer with endothelin receptor antagonists. Clin Cancer Res 12: S6296–S6300

    Google Scholar 

  74. Nelson JB et al. (2003) Suppression of prostate cancer induced bone remodeling by the endothelin receptor A antagonist atrasentan. J Urol 169: 1143–1149

    CAS  PubMed  Google Scholar 

  75. Body JJ et al. (2003) A phase I study of AMGN-0007, a recombinant osteoprotegerin construct, in patients with multiple myeloma or breast carcinoma related bone metastases. Cancer 97: 887–892

    PubMed  Google Scholar 

  76. Body JJ et al. (2006) A study of the biological receptor activator of nuclear factor-kappaB ligand inhibitor, denosumab, in patients with multiple myeloma or bone metastases from breast cancer. Clin Cancer Res 12: 1221–1228

    CAS  PubMed  Google Scholar 

  77. Palmieri D et al. (2005) Medroxyprogesterone acetate elevation of Nm23-H1 metastasis suppressor expression in hormone receptor-negative breast cancer. J Natl Cancer Inst 97: 632–642

    CAS  PubMed  Google Scholar 

  78. Titus B et al. (2005) Endothelin axis is a target of the lung metastasis suppressor gene RhoGDI2. Cancer Res 65: 7320–7327

    CAS  PubMed  Google Scholar 

  79. Horak C et al. (2007) Nm23-H1 suppresses metastasis by inhibiting expression of the lysophosphatidic acid receptor EDG2. Cancer Res 67: 11751–11759

    CAS  PubMed  Google Scholar 

  80. Orsini MJ et al. (2007) Metastin (KiSS-1) mimetics identified from peptide structure-activity relationship-derived pharmacophores and directed small molecule database screening. J Med Chem 50: 462–471

    CAS  PubMed  Google Scholar 

  81. Gupta GP et al. (2007) Mediators of vascular remodelling co-opted for sequential steps in lung metastasis. Nature 446: 765–770

    CAS  PubMed  Google Scholar 

  82. Kang Y et al. (2005) Breast cancer bone metastasis mediated by the Smad tumor suppressor pathway. Proc Natl Acad Sci USA 102: 13909–13914

    CAS  PubMed  PubMed Central  Google Scholar 

  83. Nam JS et al. (2006) Bone sialoprotein mediates the tumor cell-targeted prometastatic activity of transforming growth factor beta in a mouse model of breast cancer. Cancer Res 66: 6327–6335

    CAS  PubMed  PubMed Central  Google Scholar 

  84. Zhang Q et al. (2006) Blockade of transforming growth factor-β signaling in tumor-reactive CD8(+) T cells activates the antitumor immune response cycle. Mol Cancer Ther 5: 1733–1743

    CAS  PubMed  Google Scholar 

  85. Biswas S et al. (2007) Inhibition of TGF-beta with neutralizing antibodies prevents radiation-induced acceleration of metastatic cancer progression. J Clin Invest 117: 1305–1313

    CAS  PubMed  PubMed Central  Google Scholar 

  86. Biswas S et al. (2006) Inhibition of transforming growth factor-beta signaling in human cancer: targeting a tumor suppressor network as a therapeutic strategy. Clin Cancer Res 12: 4142–4146

    CAS  PubMed  Google Scholar 

  87. Ono K et al. (2006) Involvement of hepatocyte growth factor in the development of bone metastasis of a mouse mammary cancer cell line, BALB/c-MC. Bone 39: 27–34

    CAS  PubMed  Google Scholar 

  88. Peruzzi B and Bottaro DP (2006) Targeting the c-Met signaling pathway in cancer. Clin Cancer Res 12: 3657–3660

    CAS  PubMed  Google Scholar 

  89. Rucci N et al. (2006) Inhibition of protein kinase c-Src reduces the incidence of breast cancer metastases and increases survival in mice: implications for therapy. J Pharmacol Exp Ther 318: 161–172

    CAS  PubMed  Google Scholar 

  90. Jallal H et al. (2007) A Src/Abl kinase inhibitor, SKI-606, blocks breast cancer invasion, growth, and metastasis in vitro and in vivo. Cancer Res 67: 1580–1588

    CAS  PubMed  Google Scholar 

  91. Al-Hajj M et al. (2003) Prospective identification of tumorigenic breast cancer cells. Proc Natl Acad Sci USA 100: 3983–3988

    CAS  PubMed  PubMed Central  Google Scholar 

  92. Jones DH et al. (2006) Regulation of cancer cell migration and bone metastasis by RANKL. Nature 440: 692–696

    CAS  PubMed  Google Scholar 

  93. Park BK et al. (2007) NF-kappaB in breast cancer cells promotes osteolytic bone metastasis by inducing osteoclastogenesis via GM-CSF. Nat Med 13: 62–69

    CAS  PubMed  Google Scholar 

  94. Horsman MR and Siemann DW (2006) Pathophysiologic effects of vascular-targeting agents and the implications for combination with conventional therapies. Cancer Res 66: 11520–11539

    CAS  PubMed  Google Scholar 

  95. Bandyopadhyay A et al. (2006) Inhibition of pulmonary and skeletal metastasis by a transforming growth factor-beta type I receptor kinase inhibitor. Cancer Res 66: 6714–6721

    CAS  PubMed  Google Scholar 

  96. Lang JY et al. (2005) Antimetastatic effect of salvicine on human breast cancer MDA-MB-435 orthotopic xenograft is closely related to Rho-dependent pathway. Clin Cancer Res 11: 3455–3464

    CAS  PubMed  Google Scholar 

  97. Palm D et al. (2006) The norepinephrine-driven metastasis development of PC-3 human prostate cancer cells in BALB/c nude mice is inhibited by beta-blockers. Int J Cancer 118: 2744–2749

    CAS  PubMed  Google Scholar 

  98. Giubellino A et al. (2007) Inhibition of tumor metastasis by a growth factor receptor bound protein 2 Src homology 2 domain-binding antagonist. Cancer Res 67: 6012–6016

    CAS  PubMed  Google Scholar 

  99. Cairns RA and Hill RP (2004) Acute hypoxia enhances spontaneous lymph node metastasis in an orthotopic murine model of human cervical carcinoma. Cancer Res 64: 2054–2061

    CAS  PubMed  Google Scholar 

  100. Cassinelli G et al. (2006) Inhibition of c-Met and prevention of spontaneous metastatic spreading by the 2-indolinone RPI-1. Mol Cancer Ther 5: 2388–2397

    CAS  PubMed  Google Scholar 

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Acknowledgements

PS Steeg was funded by the Intramural research program of the Center for Cancer Research, NCI, and D Theodorescu was supported by NIH grants CA104106 and CA075115.

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Correspondence to Patricia S Steeg or Dan Theodorescu.

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Supplementary information

Supplementary Table 1

Selected reports comparing primary tumors and metastases (DOC 101 kb)

Supplementary Table 2

Selected preclinical studies for bone metastasis (DOC 66 kb)

Supplementary Table 3

Selected anti-angiogenesis clinical trials in the metastatic setting (DOC 54 kb)

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Steeg, P., Theodorescu, D. Metastasis: a therapeutic target for cancer. Nat Rev Clin Oncol 5, 206–219 (2008). https://doi.org/10.1038/ncponc1066

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