Antiangiogenesis

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Antiangiogenesis is a medical term . Literally translated, the term means directed against vessel formation . It is used to describe the medicinal method used to curb the formation of blood vessels ( angiogenesis ) in tumor and other diseases. This prevents tumors from growing.

Diseases

A therapy by antiangiogenesis is possible with different clinical pictures.

Tumor diseases

If malignant solid tumors exceed a size of a few millimeters, the cancerous tumors can no longer absorb enough oxygen and nutrients from the surrounding tissue : they need their own blood vessels in order to continue to grow and to be able to form metastases. Angiogenesis is - in healthy tissue and in tumors - by biological growth and control factors, e.g. B. VEGF ( vascular endothelial growth factor ) regulated. If the formation of new blood vessels does not occur in tumors, the state of tumor dormancy is reached. Since this is a targeted inhibition of angiogenesis, it is called targeted therapy ( targeted therapy ).

Other diseases

In one study, bevacizumab was used to treat vascular malformations of the liver in patients with HHT (hereditary hemorrhagic telangiectasia, Osler's disease). The treatment of arteriovenous vascular malformations of the brain with bevacizumab is promised after promising experiments in the mouse model .

Inhibitors of angiogenesis (including ranibizumab, bevacizumab) are also used as medicaments for wet macular degeneration, the pathomechanism of which also depends on angiogenesis.

history

As early as the 1970s, the American cancer researcher Judah Folkman developed the model concept that one could also inhibit cancer growth by blocking this angiogenesis . This led to the idea of ​​starving out tumors and “disconnecting them” from the patient's body - antiangiogenesis.

However, the road from model to therapy was long: many steps in the formation of blood vessels have not yet been identified. Several natural control factors are now known that regulate the "stop-and-go" in vein growth, such as the vascular growth factor VEGF ( Vascular Endothelial Growth Factor ). Some artificial substances also intervene in angiogenesis. They are difficult to identify, manufacture or genetically engineer and purify. The first genetically engineered angiogenesis inhibitor approved for medical use was the VEGF antibody bevacizumab .

Substances

Bevacizumab

The humanized monoclonal antibody bevacizumab inhibits the angiogenesis of tumors by binding and neutralizing the vascular growth factor VEGF released by the tumor. A threefold mechanism of action is postulated for this targeted VEGF inhibition:

  • newly formed, immature blood vessels recede
  • the formation of new vessels is prevented
  • the permeability of mature blood vessels is normalized, so that the chemotherapeutic agents used in combination with bevacizumab reach the tumor better and thus have a more targeted effect

Bevacizumab is approved as a drug for the treatment of the following cancers under the trade name Avastin (Roche Pharma AG): colon cancer, lung cancer, breast cancer , renal cell cancer and ovarian cancer. The effectiveness of bevacizumab in other tumors (e.g. glioblastoma) is being studied.

Aflibercept

Aflibercept (trade name Eylea ® ; manufacturer Bayer HealthCare or. Zaltrap ® ; manufacturer Sanofi ) is a new recombinant growth factor inhibitor for the treatment of age-related macular degeneration (AMD) resp. of metastatic colorectal cancer (mCRC) . Even if the drug was the pharmaceutical company's new hope, new benefit assessments now show that aflibercept does not bring any additional benefit for the treatment of macular edema.

Since 2011, newly approved drugs with new active ingredients have had to undergo an " early benefit assessment " by the Federal Joint Committee (G-BA) based on Section 35a SGB ​​V ( AMNOG ) if the pharmaceutical manufacturer wants to achieve a sales price that is higher than the annual therapy costs for the comparative therapy leads or is above a possible fixed amount . Only if there is an additional benefit can the pharmaceutical manufacturer negotiate a price with the umbrella association of statutory health insurance companies. This also applied to aflibercept. In the regular course of the procedure, the Institute for Quality and Efficiency in Health Care (IQWiG) initially issued an assessment: No evidence of additional benefit. Manufacturer dossier contains no usable data for comparison with ranibizumab .

swell

  1. ^ N. Almog: Molecular mechanisms underlying tumor dormancy. In: Cancer Lett 294, 2010, pp. 139-146. PMID 20363069
  2. Bevacizumab in Patients With Hereditary Hemorrhagic Telangiectasia and Severe Hepatic Vascular Malformations and High Cardiac Output. (Freely available article) March 7, 2012 .
  3. Bevacizumab Attenuates VEGF-Induced Angiogenesis and Vascular Malformations in the Adult Mouse Brain, Stroke Journal, May 8, 2012 .
  4. CG Willet et al .: Direct evidence that the VEGF-specific antibody bevacizumab has antivascular effects in human rectal cancer. In: Nature medicine. Volume 10, number 2, February 2004, pp. 145-147, doi : 10.1038 / nm988 , PMID 14745444 , PMC 2693485 (free full text).
  5. MR Mancuso et al.: Rapid vascular regrowth in tumors after reversal of VEGF inhibition. In: The Journal of clinical investigation. Volume 116, number 10, October 2006, pp. 2610-2621, doi : 10.1172 / JCI24612 , PMID 17016557 , PMC 1578604 (free full text).
  6. Jain et al.: Normalization of tumor vasculature: an emerging concept in antiangiogenic therapy. In: Science 307, 2005, pp. 58-62. PMID 15637262
  7. New Perspectives in Advanced Ovarian Cancer: Approval for Bevacizumab, January 19, 2012 .
  8. New medicines Eylea ® (Aflibercept) (PDF; 132 kB) Information from the Medicines Commission of the German Medical Association (AkdÄ) , as of February 28, 2013.
  9. New on the market: Aflibercept in Macular Degeneration DAZ from January 16, 2013, accessed on March 1, 2013.
  10. New drugs Zaltrap ® (Aflibercept) (PDF; 852 kB) Information from the drug commission of the German medical profession (AkdÄ), as of May 22, 2013.
  11. aflibercept - Benefit assessment according to § 35a SGB V .
  12. Aflibercept in macular edema: added benefit not proven .
  13. No evidence for additional benefits ( Memento of the original dated December 6, 2014 in the Internet Archive ) Info: The archive link was inserted automatically and has not yet been checked. Please check the original and archive link according to the instructions and then remove this notice. , PM of the Institute for Quality and Efficiency in Health Care from March 15, 2013. @1@ 2Template: Webachiv / IABot / www.iqwig.de