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Avastin MoA

Avastin (bevacizumab)

Angiogenesis is the process of new blood vessel formation. It is an important process in the growth of malignant tumours as tumours need to establish their own blood supply to grow beyond 1–2mm in diameter. The predominant regulator of tumour angiogenesis is VEGF,1,2 which is the only angiogenic factor known to be present throughout the entire tumour life cycle.3,4 This continuous expression, along with the proposed genetic stability of VEGF and endothelial cells (based on preclinical observations),2,5 make direct and continuous targeting of VEGF an important antitumour strategy.3

   

Avastin is a humanised MAb with a long half life that specifically inhibits VEGF, thus blocking the angiogenic cascade. Avastin was developed from the murine anti-VEGF MAb A4.6.16 and recognises all major isoforms of human VEGF.

  

Avastin exerts its anti-angiogenic effects through three key mechanisms.

  1. Regression of tumour vasculature.7,8
  2. Normalisation of surviving vasculature.8,9
  3. Inhibition of new and recurrent vessel growth.10,11
 

Each of these effects will be explored in more detail in the following pages.

 

Given the central role of angiogenesis in tumour development, anti-angiogenic agents should be considered a pillar of anticancer therapy, alongside surgery, radiotherapy and chemotherapy (and hormonal therapy).

 

To learn more about precise VEGF inhibition with Avastin, click here or navigate using the links provided.

 

References

  1. Ferrara N. Endocr Rev 2004;25:581–611.
  2. Hicklin DJ, Ellis LM. J Clin Oncol 2005;23:1011–27.
  3. Folkman J. In: DeVita VT, Hellman SMD, Rosenberg SA, editors. Cancer: principles and practice of oncology. 7th ed. Philadelphia: Lippincott Williams & Wilkins, 2005. p. 2865–82.
  4. Daniele G, Marciano R, Tortora G. EJC Suppl 2008;6:26–29.
  5. Mukhopadhyay D, Datta K. Semin Cancer Biol 2004;14:123–30.
  6. Presta LG, Chen H, O'Connor SJ, et al. Cancer Res 1997;57:4593–9.
  7. Yuan F, Chen Y, Dellian M, Safabakhsh N, Ferrara N, Jain RK. Proc Natl Acad Sci USA 1996;93:14765–70.
  8. Willett CG, Boucher Y, di Tomaso TE, et al. Nat Med 2004;10:145–7.
  9. Gerber HP, Ferrara N. Cancer Res 2005;65:671–80.
  10. Borgström P, Hillan KJ, Sriramarao P, Ferrara N. Cancer Res 1996;56:4032–9.
  11. Borgström P, Bourdon MA, Hillan KJ, Sriramarao P, Ferrara N. Prostate 1998;35:1–10.

Avastin TV

Watch Dr Fairooz Kabbinavar as he presented “Controlling angiogenesis to control tumour growth” at the Anti-angiogenesis Clinical Experience Exchange Meeting held in Madrid, Spain in April 2009.

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