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End of the road: confounding results of the CORE trial terminate the arduous journey of cilengitide for glioblastoma


Al Musella's Comments: (This is his personal views and are not necessarily the views of the Musella Foundation!)

 This is sadly the end of the drug Cilengitide. We all had high hopes for it. They tried many different combinations and all of the trials failed, so they are giving up on it.  It is sad because it seemed to make a lot of sense, which we thought would translate into a benefit but it didn't work out. 



Website: http://neuro-oncology.oxfordjournals.org/content/early/2015/02/13/neuonc.nov018.extract

Posted on: 02/21/2015

 

End of the road: confounding results of the CORE trial terminate the arduous journey of cilengitide for glioblastoma

  1. Warren P. Mason

+Author Affiliations

  1. Department of MedicinePrincess Margaret Cancer Centre and University of Toronto
  1. Corresponding Author: Warren P. Mason, MD, Princess Margaret Cancer Centre, 610 University Avenue, Suite 18-717, Toronto, ON M5G 2M9 (warren.mason@uhn.ca).
  • Received January 18, 2015.
  • Accepted January 19, 2015.

The integrin family of cell adhesion receptors has been studied extensively in cancer and is implicated in tumor cell survival, migration, proliferation, and angiogenesis.1 These transmembrane receptors, composed of dimerized α and B domains, play a crucial role in how tumor cells communicate with the microenvironment through a multiplicity of interactions with numerous extracellular ligands via an arginine-glycine-aspartic acid (RDG) peptide. Integrins are involved in the regulation of tumor cell growth, but their role is complex and incompletely understood. There is evidence that these receptors influence tumor cell survival in both ligated and unligated states in often contradictory ways. Integrins are apparently involved in the biology of glioblastoma, where αvB3 and to a lesser extent αvB5 integrins are expressed at increased levels at the interface of the tumor and normal tissues, including angiogenic endothelial and glioblastoma cells, where they have a putative role in invasion, angiogenesis, and growth factor–mediated cell survival.2Furthermore, the αvB3 ligand vitronectin is expressed in glioblastoma extracellular matrix where potential interactions with surrounding integrins can influence tumor cell survival and invasion.3

Cilengitide, a cyclic RDG peptide that inhibits both αvB3 and αvB5 integrins, has received rigorous and thoughtful evaluation in glioblastoma as a novel therapeutic targeting the tumor microenvironment. …

 




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