New article is published by the team from MSK incl.Ladanyi reg. role of the
MET receptor tyrosine kinase gene, they found it to be over expressed in ASPS and possible to use as a potential therapeutic target.
This is the link to the abstract on the Pubmed.gov (it's ID is 17283122 - you can search it by this number):
TFE3 Fusions Activate MET Signaling by Transcriptional Up-regulation, Defining Another Class of Tumors as Candidates for Therapeutic MET Inhibition.
http://www.ncbi.nlm.nih.gov/entrez/quer ... med_docsum
The say that:
the MET receptor tyrosine kinase gene as significantly overexpressed in ASPS relative to four other types of primitive sarcomas. We therefore examined MET as a direct transcriptional target of ASPL-TFE3. ASPL-TFE3 binds to the MET promoter and strongly activates it. Induction of MET by ASPL-TFE3 results in strong MET autophosphorylation and activation of downstream signaling in the presence of hepatocyte growth factor (HGF). Inhibiting MET by RNA interference or by the inhibitor PHA665752 abolishes HGF-dependent MET activation, causing decreased cell growth and loss of HGF-dependent phenotypes. MET is thus a potential therapeutic target.
MET Signaling as a potential therapeutic target
There was a dear child who participatred in a clinical trial of TNP-470 at MSK in 1999. She had a response, however, although her lung tumors began to shrink, she subsequently presented with tumors in her spine and rib, and sadly, passed away later in that year. Now, PPI-2458, "structurally related to fumagillin and TNP-470" and "designed to overcome the clinical limitations of TNP-470" is in clinical trial http://www.cancer.gov/search/ViewClinic ... id=3047490
I would hope that the research will be studied by those of us in this group who understand the scientific details (I am certainly not one of them) and if they find that PPI-2458 is a rational drug to try as treatment for asps, that they help us and our doctors to gain access to this drug, if not through the trials but through any other means. There is a Web powerpoint from which I quoted at http://library.corporate-ir.net/library ... 092105.pdf
thanks so much, Olga, Beth
I would hope that the research will be studied by those of us in this group who understand the scientific details (I am certainly not one of them) and if they find that PPI-2458 is a rational drug to try as treatment for asps, that they help us and our doctors to gain access to this drug, if not through the trials but through any other means. There is a Web powerpoint from which I quoted at http://library.corporate-ir.net/library ... 092105.pdf
thanks so much, Olga, Beth