Research and Development

Inhibition of angiogenesis and metastasis

The formation of blood vessels from pre-existing vessels (angiogenesis) is a central mechanism in the human organism. Angiogenesis is of particular importance in cancer during the formation of primary tumors and metastases.

amcure’s series of compounds differs from currently available angiogenesis inhibitors that specifically address only one receptor tyrosine kinase e.g. VEGFR or one growth factor e.g. VEGF. The peptide based substances target the tumor specific co-receptor CD44v6 which is a prerequisite for the activation of several RTKs. They are first-in-class inhibitors with a significantly improved specificity compared to other substances currently available on the market. The product candidates inhibit both the VEGF/VEGF-R and the HGF/c-Met pathway, which are both instrumental for angiogenesis.

Benefits

Efficacy

  • The use of our compounds inhibits the development of metastases and is currently the only way to induce a regression of already developed metastases in different cancer types.
  • Inhibition of this co-receptor and subsequent blocking of two important angiogenesis pathways abrogates the activation of escape mechanisms in the tumor.

Safety

  • The compounds are based on a short sequence of natural amino acids. A good tolerance and a moderate or no immugenicity is expected also from a modified compound.
  • Inhibition of CD44v6 is a promising therapeutic option to inhibit angiogenesis and metastasis in a more selective way than available therapies.

Posters

Related publications

Inhibition of Tumor Growth and Metastasis in Pancreatic Cancer Models by Interference With CD44v6 Signaling. Matzke-Ogi A, Jannasch K, Shatirishvili M, Fuchs B, Chiblak S, Morton J, Tawk B, Lindner T, Sansom O, Alves F, Warth A, Schwager C, Mier W, Kleeff J, Ponta H, Abdollahi A, Orian-Rousseau V., Gastroenterology. 2016 Feb;150(2):513-25. Epub 2015 Oct 24.

CD44, a therapeutic target for metastasising tumours. Orian-Rousseau V., Eur J Cancer. 2010 May;46(7):1271-7. Epub 2010 Mar 19. Review.

A CD44v6 peptide reveals a role of CD44 in VEGFR-2 signaling and angiogenesis. Tremmel M, Matzke A, Albrecht I, Laib AM, Olaku V, Ballmer-Hofer K, Christofori G, Héroult M, Augustin HG, Ponta H, Orian-Rousseau V., Blood. 2009 Dec 10;114(25):5236-44. Epub .

Involvement of CD44v6 in InlB-dependent Listeria invasion. Jung C, Matzke A, Niemann HH, Schwerk C, Tenenbaum T, Orian-Rousseau V., Mol Microbiol. 2009 Jun;72(5):1196-207. Epub 2009 Apr 30.

A five-amino-acid peptide blocks Met- and Ron-dependent cell migration. Matzke A, Herrlich P, Ponta H, Orian-Rousseau V., Cancer Res. 2005 Jul 15;65(14):6105-10.

CD44 is required for two consecutive steps in HGF/c-Met signaling. Orian-Rousseau V, Chen L, Sleeman JP, Herrlich P, Ponta H. Genes Dev. 2002 Dec 1;16(23):3074-86.

Hyaluronate-independent metastatic behavior of CD44 variant-expressing pancreatic carcinoma cells. Sleeman JP, Arming S, Moll JF, Hekele A, Rudy W, Sherman LS, Kreil G, Ponta H, Herrlich P. Cancer Res. 1996 Jul 1;56(13):3134-41.

CD44: structure, function, and association with the malignant process. Naor D, Sionov RV, Ish-Shalom D. Adv Cancer Res. 1997;71:241-319.

CD44 splice variants as prognostic markers in colorectal cancer. Wielenga VJ, van der Voort R, Mulder JW, Kruyt PM, Weidema WF, Oosting J, Seldenrijk CA, van Krimpen C, Offerhaus GJ, Pals ST. Scand J Gastroenterol. 1998 Jan;33(1):82-7.

A new variant of glycoprotein CD44 confers metastatic potential to rat carcinoma cells. Günthert, U., Hofmann, M., Rudy, W., Reber, S., Zöller, M., Haußmann, I., Matzku, S., Wenzel, A., Ponta, H., and Herrlich, P. (1991). Cell 65, 13-24.