Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Biomarkers of response and resistance to antiangiogenic therapy

Abstract

No validated biological markers (or biomarkers) currently exist for appropriately selecting patients with cancer for antiangiogenic therapy. Nor are there biomarkers identifying escape pathways that should be targeted after tumors develop resistance to a given antiangiogenic agent. A number of potential systemic, circulating, tissue and imaging biomarkers have emerged from recently completed phase I–III studies. Some of these are measured at baseline (for example VEGF polymorphisms), others are measured during treatment (such as hypertension, MRI-measured Ktrans, circulating angiogenic molecules or collagen IV), and all are mechanistically based. Some of these biomarkers might be pharmacodynamic (for example, increase in circulating VEGF, placental growth factor) while others have potential for predicting clinical benefit or identifying the escape pathways (for example, stromal-cell-derived factor 1α, interleukin-6). Most biomarkers are disease and/or agent specific and all of them need to be validated prospectively. We discuss the current challenges in establishing biomarkers of antiangiogenic therapy, define systemic, circulating, tissue and imaging biomarkers and their advantages and disadvantages, and comment on the future opportunities for validating biomarkers of antiangiogenic therapy.

Key Points

  • There are no validated biomarkers for selecting patients who will respond to antiangiogenic therapy; however, a number of systemic, circulating, tissue and imaging biomarkers are emerging and need to be prospectively validated

  • Antiangiogenic therapy can prune tumor vessels and 'normalize' the remaining vasculature, which decreases vessel diameter, vascular basement membrane thickness, vascular permeability, interstitial fluid pressure and increases pericyte coverage

  • A 'vascular normalization index' is associated with increased overall survival in patients with recurrent glioblastoma treated with cediranib, a pan-VEGFR tyrosine kinase inhibitor

  • Baseline levels of VEGF in tumors or the circulation seem to correlate with the outcome for some disease-agent combinations (bevacizumab with chemotherapy in metastatic breast cancer) but not others (metastatic colorectal cancer)

  • The most prevalent toxic effect of antiangiogenic therapy is hypertension, which when severe might be associated with certain genotypes but also with a better outcome in patients with metastatic breast cancer

  • VEGF and placental growth factor levels increase after anti-angiogenic treatment, but other biomarkers are associated with poor outcome, which suggests that these pathways have a role in resistance to anti-VEGF therapies

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Candidate biomarkers of response and resistance to antiangiogenic therapy.
Figure 2: Modes of vessel recruitment to tumors that might be involved in tumor escape from antiangiogenic therapy.

Similar content being viewed by others

References

  1. Carmeliet, P. & Jain, R. K. Angiogenesis in cancer and other diseases. Nature 407, 249–257 (2000).

    Article  CAS  PubMed  Google Scholar 

  2. Jain, R. K. Molecular regulation of vessel maturation. Nat. Med. 9, 685–693 (2003).

    Article  CAS  PubMed  Google Scholar 

  3. Folkman, J. Tumor angiogenesis: therapeutic implications. N. Engl. J. Med. 285, 1182–1186 (1971).

    Article  CAS  PubMed  Google Scholar 

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

    Article  CAS  PubMed  Google Scholar 

  5. Miller, K. et al. Paclitaxel plus bevacizumab versus paclitaxel alone for metastatic breast cancer. N. Engl. J. Med. 357, 2666–2676 (2007).

    Article  CAS  PubMed  Google Scholar 

  6. Rini, B. I. et al. Bevacizumab plus interferon alfa compared with interferon alfa monotherapy in patients with metastatic renal cell carcinoma: CALGB 90206. J. Clin. Oncol. 26, 5422–5328 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Sandler, A. et al. Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer. N. Engl. J. Med. 355, 2542–2550 (2006).

    Article  CAS  PubMed  Google Scholar 

  8. Escudier, B. et al. Sorafenib in advanced clear-cell renal-cell carcinoma. N. Engl. J. Med. 356, 125–134 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Motzer, R. J. et al. Sunitinib versus interferon alfa in metastatic renal-cell carcinoma. N. Engl. J. Med. 356, 115–124 (2007).

    Article  CAS  PubMed  Google Scholar 

  10. Llovet, J. M. et al. Sorafenib in advanced hepatocellular carcinoma. N. Engl. J. Med. 359, 378–390 (2008).

    Article  CAS  PubMed  Google Scholar 

  11. Giantonio, B. J. et al. Bevacizumab in combination with oxaliplatin, fluorouracil, and leucovorin (FOLFOX4) for previously treated metastatic colorectal cancer: results from the Eastern Cooperative Oncology Group Study E3200. J. Clin. Oncol. 25, 1539–1544 (2007).

    Article  CAS  PubMed  Google Scholar 

  12. Demetri, G. D. et al. Efficacy and safety of sunitinib in patients with advanced gastrointestinal stromal tumour after failure of imatinib: a randomised controlled trial. Lancet 368, 1329–1338 (2006).

    Article  CAS  PubMed  Google Scholar 

  13. Hughes, B. (2007). Novel risk-sharing scheme puts the spotlight on biomarkers. Nat. Rev. Drug Discov. 6, 945.

    Article  CAS  Google Scholar 

  14. Sinha, G. Expensive cancer drugs with modest benefit ignite debate over solutions. J. Natl. Cancer Inst. 100, 1347–1349 (2008).

    Article  PubMed  Google Scholar 

  15. Karapetis, C. S. et al. K-ras mutations and benefit from cetuximab in advanced colorectal cancer. N. Engl. J. Med. 359, 1757–1765 (2008).

    Article  CAS  PubMed  Google Scholar 

  16. Oldenhuis, C. N., Oosting, S. F., Gietema, J. A. & de Vries, E. G. Prognostic versus predictive value of biomarkers in oncology. Eur. J. Cancer 44, 946–953 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. McShane, L. M. et al. Reporting recommendations for tumor marker prognostic studies (REMARK). Nat. Clin. Pract. Oncol. 2, 416–422 (2005).

    CAS  PubMed  Google Scholar 

  18. Batchelor, T. T. et al. AZD2171, a pan-VEGF receptor tyrosine kinase inhibitor, normalizes tumor vasculature and alleviates edema in glioblastoma patients. Cancer Cell 11, 83–95 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ebos, J. M., Lee, C. R., Christensen, J. G., Mutsaers, A. J. & Kerbel, R. S. Multiple circulating proangiogenic factors induced by sunitinib malate are tumor-independent and correlate with antitumor efficacy. Proc. Natl Acad. Sci. USA 104, 17069–17074 (2007).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Kamoun, W. S. et al. Edema control by cediranib, a vascular endothelial growth factor receptor-targeted kinase inhibitor, prolongs survival despite persistent brain tumor growth in mice. J. Clin. Oncol. doi:10.1200/JCO.2008.19.9356 (2009).

  21. Norden-Zfoni, A. et al. Blood-based biomarkers of SU11248 activity and clinical outcome in patients with metastatic imatinib-resistant gastrointestinal stromal tumor. Clin. Cancer Res. 13, 2643–2650 (2007).

    Article  CAS  PubMed  Google Scholar 

  22. Willett, C. G. et al. Efficacy, safety and biomarkers of neoadjuvant bevacizumab, radiation therapy and 5-Fluorouracil in rectal cancer: a multidisciplinary phase II study. J. Clin. Oncol. doi:10.1200/JCO.2008.21.1771 (2009).

  23. Zhu, A. X. et al. Efficacy, safety and potential biomarkers of sunitinib monotherapy in advanced hepatocellular carcinoma: A phase II study. J. Clin. Oncol. doi: 10.1200/jco.2008.20.9908

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Crabb, S. J. et al. Tumor cavitation: impact on objective response evaluation in trials of angiogenesis inhibitors in non-small-cell lung cancer. J. Clin. Oncol. 27, 404–410 (2009).

    Article  CAS  PubMed  Google Scholar 

  25. Hudis, C. A. Trastuzumab—mechanism of action and use in clinical practice. N. Engl. J. Med. 357, 39–51 (2007).

    Article  CAS  PubMed  Google Scholar 

  26. Cameron, D. A. & Stein, S. Drug Insight: intracellular inhibitors of HER2--clinical development of lapatinib in breast cancer. Nat. Clin. Pract. Oncol. 5, 512–520 (2008).

    Article  CAS  PubMed  Google Scholar 

  27. Carmeliet, P. Angiogenesis in life, disease and medicine. Nature 438, 932–936 (2005).

    Article  CAS  PubMed  Google Scholar 

  28. Jain, R. K., Duda, D. G., Clark, J. W. & Loeffler, J. S. Lessons from phase III clinical trials on anti-VEGF therapy for cancer. Nat. Clin. Pract. Oncol. 3, 24–40 (2006).

    Article  CAS  PubMed  Google Scholar 

  29. Jain, R. K. Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. Science 307, 58–62 (2005).

    Article  CAS  PubMed  Google Scholar 

  30. Winkler, F. et al. Kinetics of vascular normalization by VEGFR2 blockade governs brain tumor response to radiation: role of oxygenation, angiopoietin-1, and matrix metalloproteinases. Cancer Cell 6, 553–563 (2004).

    CAS  PubMed  Google Scholar 

  31. Willett, C. G. et al. Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. Nat. Med. 10, 145–147 (2004).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Willett, C. G. et al. Surrogate markers for antiangiogenic therapy and dose-limiting toxicities for bevacizumab with radiation and chemotherapy: continued experience of a phase I trial in rectal cancer patients. J. Clin. Oncol. 23, 8136–8139 (2005).

    Article  PubMed  Google Scholar 

  33. Kerbel, R. S. Tumor angiogenesis. N. Engl. J. Med. 358, 2039–2049 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Rini, B. I. et al. Association of diastolic blood pressure (dBP) ≥90 mmHg with overall survival (OS) in patients treated with axitinib (AG-013736) [Abstract]. ASCO Meeting Abstracts 26, 3543 (2008).

    Google Scholar 

  35. Shojaei, F. et al. Tumor refractoriness to anti-VEGF treatment is mediated by CD11b+Gr1+ myeloid cells. Nat. Biotechnol. 25, 911–920 (2007).

    Article  CAS  PubMed  Google Scholar 

  36. Hamzah, J. et al. Vascular normalization in Rgs5-deficient tumours promotes immune destruction. Nature 453, 410–414 (2008).

    Article  CAS  PubMed  Google Scholar 

  37. Batchelor, T. T. et al. A multidisciplinary phase II study of AZD2171 (cediranib), an oral pan-VEGF receptor tyrosine kinase inhibitor, in patients with recurrent glioblastoma [Abstract]. AACR Meeting Abstracts LB-247 (2008).

  38. Schneider, B. P. et al. Association of vascular endothelial growth factor and vascular endothelial growth factor receptor-2 genetic polymorphisms with outcome in a trial of paclitaxel compared with paclitaxel plus bevacizumab in advanced breast cancer: ECOG 2100. J. Clin. Oncol. 26, 4672–4678 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Burstein, H. J. et al. VEGF as a marker for outcome among advanced breast cancer patients receiving anti-VEGF therapy with bevacizumab and vinorelbine chemotherapy. Clin. Cancer Res. 14, 7871–7877 (2008).

    Article  CAS  PubMed  Google Scholar 

  40. Jubb, A. M. et al. 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 (2006).

    Article  CAS  PubMed  Google Scholar 

  41. Dowlati, A., Gray, R., Sandler, A. B., Schiller, J. H. & Johnson, D. H. Cell adhesion molecules, vascular endothelial growth factor, and basic fibroblast growth factor in patients with non-small cell lung cancer treated with chemotherapy with or without bevacizumab—an Eastern Cooperative Oncology Group Study. Clin. Cancer Res. 14, 1407–1412 (2008).

    Article  CAS  PubMed  Google Scholar 

  42. Jain, R. K. Lessons from multidisciplinary translational trials on anti-angiogenic therapy of cancer. Nat. Rev. Cancer 8, 309–316 (2008).

    Article  CAS  PubMed  Google Scholar 

  43. 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, 391–400 (2004).

    Article  CAS  PubMed  Google Scholar 

  44. Dvorak, H. F. Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J. Clin. Oncol. 20, 4368–4380 (2002).

    Article  CAS  PubMed  Google Scholar 

  45. Sorensen, A. G., Batchelor, T. T., Wen, P. Y., Zhang, W. T. & Jain, R. K. Response criteria for glioma. Nat. Clin. Pract. Oncol. 5, 634–644 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  46. Heymach, J. V. et al. Baseline VEGF as a potential predictive biomarker of vandetanib clinical benefit in patients with advanced NSCLC [Abstract]. ASCO Meeting Abstracts 26, 8009 (2008).

    Google Scholar 

  47. Tannir, N. M. et al. A randomized phase II trial of sorafenib versus sorafenib plus low-dose interferon-alfa: Clinical results and biomarker analysis [Abstract]. ASCO Meeting Abstracts 26, 5093 (2008).

    Google Scholar 

  48. Rini, B. I. et al. Antitumor activity and biomarker analysis of sunitinib in patients with bevacizumab-refractory metastatic renal cell carcinoma. J. Clin. Oncol. 26, 3743–3748 (2008).

    Article  CAS  PubMed  Google Scholar 

  49. Deprimo, S. E. et al. Circulating protein biomarkers of pharmacodynamic activity of sunitinib in patients with metastatic renal cell carcinoma: modulation of VEGF and VEGF-related proteins. J. Transl. Med. 5, 32 (2007).

    Article  PubMed  PubMed Central  Google Scholar 

  50. Drevs, J. et al. Phase I clinical study of AZD2171, an oral vascular endothelial growth factor signaling inhibitor, in patients with advanced solid tumors. J. Clin. Oncol. 25, 3045–3054 (2007).

    Article  CAS  PubMed  Google Scholar 

  51. Mita, M. M. et al. A phase II, pharmacokinetic, and biologic study of semaxanib and thalidomide in patients with metastatic melanoma. Cancer Chemother. Pharmacol. 59, 165–174 (2007).

    Article  CAS  PubMed  Google Scholar 

  52. Motzer, R. J. et al. Activity of SU11248, a multitargeted inhibitor of vascular endothelial growth factor receptor and platelet-derived growth factor receptor, in patients with metastatic renal cell carcinoma. J. Clin. Oncol. 24, 16–24 (2006).

    Article  CAS  PubMed  Google Scholar 

  53. Saltz, L. B. et al. Phase II trial of sunitinib in patients with metastatic colorectal cancer after failure of standard therapy. J. Clin. Oncol. 25, 4793–4799 (2007).

    Article  CAS  PubMed  Google Scholar 

  54. Fischer, C. et al. Anti-PlGF inhibits growth of VEGF(R)-inhibitor-resistant tumors without affecting healthy vessels. Cell 131, 463–475 (2007).

    Article  CAS  PubMed  Google Scholar 

  55. Verheul, H. M. et al. Platelets take up the monoclonal antibody bevacizumab. Clin. Cancer Res. 13, 5341–5347 (2007).

    Article  CAS  PubMed  Google Scholar 

  56. Ebos, J. M. et al. Accelerated metastasis after short-term treatment with a potent inhibitor of tumor angiogenesis. Cancer Cell 15, 232–239 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Phase III C-08 study of Avastin in early-stage colon cancer does not meet primary endpoint [online], http://www.roche.com/media_releases/med-cor-009-04-22.htm (2009).

  58. Horowitz, N. S. et al. A multidisciplinary phase II study of bevacizumab combined with oxaliplatin, gemcitabine in women with recurrent mullerian carcinoma [Abstract]. AACR Annual Abstracts 4484 (2008).

  59. Ince, W. L. et al. Association of k-ras, b-raf, and p53 status with the treatment effect of bevacizumab. J. Natl Cancer Inst. 97, 981–989 (2005).

    Article  CAS  PubMed  Google Scholar 

  60. Wilson, P. M. et al. Use of intratumoral mRNA expression of genes involved in angiogenesis and HIF1 pathway to predict outcome to VEGFR tyrosine kinase inhibitor in patients enrolled in CONFIRM1 and CONFIRM2 [Abstract]. ASCO Meeting Abstracts 26, 4002 (2008).

    Google Scholar 

  61. Kohne, C. et al. Final results of CONFIRM 2: A multinational, randomized, double-blind, phase III study in 2nd line patients with metastatic colorectal cancer receiving FOLFOX4 and PTK787/ZK 222584 (PTK/ZK) or placebo [Abstract]. ASCO Meeting Abstracts 25, 4033 (2007).

    Google Scholar 

  62. Schultheis, A. M. et al. Polymorphisms and clinical outcome in recurrent ovarian cancer treated with cyclophosphamide and bevacizumab. Clin. Cancer Res. 14, 7554–7563 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Loges, S., Mazzone, M., Hohensinner, P. & Carmeliet, P. Silencing or fueling metastasis with VEGF inhibitors: antiangiogenesis revisited. Cancer Cell 15, 167–170 (2009).

    Article  CAS  PubMed  Google Scholar 

  64. Paez-Ribes, M. et al. Antiangiogenic therapy elicits malignant progression of tumors to increased local invasion and distant metastasis. Cancer Cell 15, 220–231 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Duda, D. G. et al. A comparative study of circulating endothelial cells (CECs) and circulating progenitor cells (CPCs) kinetics in four multidisciplinary phase 2 studies of antiangiogenic agents [Abstract]. ASCO Meeting Abstracts 26, 3544 (2008).

    Google Scholar 

  66. Patterson, D. M., Padhani, A. R. & Collins, D. J. Technology insight: water diffusion MRI—a potential new biomarker of response to cancer therapy. Nat. Clin. Pract. Oncol. 5, 220–233 (2008).

    Article  PubMed  Google Scholar 

  67. Hamstra, D. A. et al. Functional diffusion map as an early imaging biomarker for high-grade glioma: correlation with conventional radiologic response and overall survival. J. Clin. Oncol. 26, 3387–3394 (2008).

    Article  PubMed  PubMed Central  Google Scholar 

  68. Sorensen, A. G. Magnetic resonance as a cancer imaging biomarker. J. Clin. Oncol. 24, 3274–3281 (2006).

    Article  PubMed  Google Scholar 

  69. Sorensen, A. G. et al. A “vascular normalization index” as potential mechanistic biomarker to predict survival after a single dose of cediranib in recurrent glioblastoma patients: Insights from a phase II study. Cancer Res. (in press).

  70. Chen, W. et al. Predicting treatment response of malignant gliomas to bevacizumab and irinotecan by imaging proliferation with [18F] fluorothymidine positron emission tomography: a pilot study. J. Clin. Oncol. 25, 4714–4721 (2007).

    Article  CAS  PubMed  Google Scholar 

  71. Tofts, P. S. et al. Estimating kinetic parameters from dynamic contrast-enhanced T(1)-weighted MRI of a diffusable tracer: standardized quantities and symbols. J. Magn. Reson. Imaging 10, 223–232 (1999).

    Article  CAS  PubMed  Google Scholar 

  72. Motzer, R. J. et al. Prognostic nomogram for sunitinib in patients with metastatic renal cell carcinoma. Cancer 113, 1552–1558 (2008).

    Article  CAS  PubMed  Google Scholar 

  73. Sandler, A. B. et al. Retrospective evaluation of the clinical and radiographic risk factors associated with severe pulmonary hemorrhage in first-line advanced, unresectable non-small-cell lung cancer treated with carboplatin and paclitaxel plus bevacizumab. J. Clin. Oncol. 27, 1405–1412 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Casanovas, O., Hicklin, D. J., Bergers, G. & Hanahan, D. Drug resistance by evasion of antiangiogenic targeting of VEGF signaling in late-stage pancreatic islet tumors. Cancer Cell 8, 299–309 (2005).

    Article  CAS  PubMed  Google Scholar 

  75. Relf, M. et al. Expression of the angiogenic factors vascular endothelial cell growth factor, acidic and basic fibroblast growth factor, tumor growth factor beta-1, platelet-derived endothelial cell growth factor, placenta growth factor, and pleiotrophin in human primary breast cancer and its relation to angiogenesis. Cancer Res. 57, 963–969 (1997).

    CAS  PubMed  Google Scholar 

  76. Yoshiji, H., Harris, S. R. & Thorgeirsson, U. P. Vascular endothelial growth factor is essential for initial but not continued in vivo growth of human breast carcinoma cells. Cancer Res. 57, 3924–3928 (1997).

    CAS  PubMed  Google Scholar 

  77. Liu, G. et al. Dynamic contrast-enhanced magnetic resonance imaging as a pharmacodynamic measure of response after acute dosing of AG-013736, an oral angiogenesis inhibitor, in patients with advanced solid tumors: results from a phase I study. J. Clin. Oncol. 23, 5464–5473 (2005).

    Article  CAS  PubMed  Google Scholar 

  78. Thomas, A. L. et al. Phase I study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of PTK787/ZK 222584 administered twice daily in patients with advanced cancer. J. Clin. Oncol. 23, 4162–4171 (2005).

    Article  CAS  PubMed  Google Scholar 

  79. Zhu, A. X. et al. Early antiangiogenic activity of bevacizumab evaluated by computed tomography perfusion scan in patients with advanced hepatocellular carcinoma. Oncologist 13, 120–125 (2008).

    Article  CAS  PubMed  Google Scholar 

  80. Yao, J. C. et al. Targeting vascular endothelial growth factor in advanced carcinoid tumor: a random assignment phase II study of depot octreotide with bevacizumab and pegylated interferon alpha-2b. J. Clin. Oncol. 26, 1316–1323 (2008).

    Article  CAS  PubMed  Google Scholar 

  81. de Bazelaire, C. et al. Magnetic resonance imaging-measured blood flow change after antiangiogenic therapy with PTK787/ZK 222584 correlates with clinical outcome in metastatic renal cell carcinoma. Clin. Cancer Res. 14, 5548–5554 (2008).

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

The authors thank the members of the Steele Lab, especially M. Ancukiewicz, Y. Boucher, E. di Tomaso, and L. Xu and M. Buyse, H. Chen, A. Grothey, C. Hudis, R. Horvitz, and A. Marshall for their helpful comments on this manuscript. The authors' work is supported by grants from the National Cancer institute P01-CA80124, P41-rr14075, R01-CA115767, R01-CA85140, R01CA126642, R21-CA99237, R21-CA117079, R01-CA129371, R01CA57683, K24-CA125440, Federal share/NCI Proton Beam Program income, M01-RR-01066, Harvard Clinical and Translational Science Center (CTSC) grant; the National Foundation for Cancer research; the Richard and Nancy Simches Endowment for Brain Tumor Research; the Montesi Family Fund; and MIND institute.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Rakesh K. Jain.

Ethics declarations

Competing interests

R. K. Jain declares he is a Consultant for AstraZenenca, Dyax, Millenium and SynDevRx. He is on the Speakers' Bureau for Pfizer and Roche, and receives grant/research support from AstraZenenca and Dyax. He is a stockholder for SynDevRx. C. G. Willett is on the Speakers' Bureau for Genentech. A. X. Zhu declares he is a consultant for Bayer and Genentech. T. T. Batchelor declares he is a consultant for Exelixis, EMD-Serono, Genentech and ImClone Systems. He receives grant/research support from AstraZeneca and Millenium, and is on the Speakers Bureau for Schering–Plough. A. G. Sorensen declares he is a consultant for AstraZeneca, Genentech and Millenium and also receives grant/research support from AstraZeneca, Genentech, Exelixis, Millenium, Novartis and Schering–Plough. The others authors declare no competing interests.

Supplementary information

Rights and permissions

Reprints and permissions

About this article

Cite this article

Jain, R., Duda, D., Willett, C. et al. Biomarkers of response and resistance to antiangiogenic therapy. Nat Rev Clin Oncol 6, 327–338 (2009). https://doi.org/10.1038/nrclinonc.2009.63

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/nrclinonc.2009.63

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing