2. Academic Validation
  3. Inhibition of both focal adhesion kinase and fibroblast growth factor receptor 2 pathways induces anti-tumor and anti-angiogenic activities

Inhibition of both focal adhesion kinase and fibroblast growth factor receptor 2 pathways induces anti-tumor and anti-angiogenic activities

  • Cancer Lett. 2014 Jun 28;348(1-2):88-99. doi: 10.1016/j.canlet.2014.03.007.
Pascal Dao 1,  Rafika Jarray 1,  Nikaia Smith 1,  Yves Lepelletier 2,  Johanne Le Coq 3,  Daniel Lietha 3,  Réda Hadj-Slimane 4,  Jean-Philippe Herbeuval 1,  Christiane Garbay 1,  Françoise Raynaud 1,  Huixiong Chen 5
Affiliations

Affiliations

  • 1 CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
  • 2 UMR CNRS 8147, Université Paris Descartes, PRES Sorbonne Paris Cité, Hôpital Necker, 149, rue de Sèvre, 75743 Paris Cedex 15, France.
  • 3 Structural Biology and Biocomputing Programme, Spanish National Cancer Research Centre (CNIO), Calle Melchor Fernández Almagro 3, Madrid 28029, Spain.
  • 4 Visiotact Pharma, 13-17, rue Moreau, 75012 Paris, France.
  • 5 CNRS, UMR8601, Laboratoire de Chimie et Biochimie Pharmacologiques et Toxicologiques, CBNIT, Université Paris Descartes, PRES Sorbonne Paris Cité, UFR Biomédicale, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France; School of Chemical Engineering and Light Industry, Guangdong University of Technology, No. 100 Waihuan Xi Road, Education Mega Center, Guangzhou 510006, China. Electronic address: huixiong.chen@parisdescartes.fr.
PMID: 24657306 DOI: 10.1016/j.canlet.2014.03.007
Abstract

FAK and FGFR2 signaling pathways play important roles in Cancer development, progression and tumor angiogenesis. PHM16 is a novel ATP competitive inhibitor of FAK and FGFR2. To evaluate the therapeutic efficacy of this agent, we examined its anti-angiogenic effect in HUVEC and its anti-tumor effect in different Cancer cell lines. We showed PHM16 inhibited endothelial cell viability, adherence and tube formation along with the added ability to induce endothelial cell Apoptosis. This compound significantly delayed tumor cell growth. Together, these data showed that inhibition of both FAK and FGFR2 signaling pathways can enhance anti-tumor and anti-angiogenic activities.

Keywords

Angiogenesis; Cancer; FAK; FGFR2; Inhibitor.

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