http://www.keystonesymposia.org/Meetings/ViewMeetings.cfm?MeetingID=810

Scroll down to Tuesday, April 11

" 5:00 - 7:00 PM Drug Targets in the Wnt Signaling
Registered attendees to this meeting can view Abstracts for this session starting on 03/07/2006 Ballroom 2-3

Paul G. Polakis, Genentech Inc.
Blockading Wnt Signaling in Colorectal Cancer

Lee L. Rubin, Curis, Inc.
Small-Molecule Inhibitors of New Wnt Signaling Components"

However, it just changed to this:

David M. Jablons, University of California, San Francisco
Developing Therapeutic Inhibitors of Wnt Signaling for Cancer Treatment: Antibodies to Small Molecules

HH,

So,based on your post,you are thinking that the new targeted area will be what we thought it might be. the WNT pathway?

If so, how does this relate to RNAi technology, if at all?

Based on my research, there are corresponding elements within recent patents pending linking DNA/CRIS to RNAi technology as well as WNT.

Any thoughts ?

Hi guest,

RNAi, fits into all of this by blocking expression of proteins or factors that are essential for tumors. So in the case of Hh you would want to nock out the expression of the Gli transcriptional proteins. There is a researcher who filed a patent for RNAi of the Gli family. Curis filed for a patent about a year latter for RNAi and the Hh pathway. None of these patents have been approved yet just filed. As for the Wnt pathway I have not been able to find any patents that are assigned to curis for the Wnt pathway.



If you search for “Wnt” and “curis” you can see back in 2001 they were interested in the Wnt pathway. The other pathways it might be are Notch and BMP-7 (antagonist). See snippet of some old news.

“Antagonists of the Hedgehog Pathway Target Cancers

Some cancers, such as basal cell carcinoma and a subset of prostate and bladder cancer, may be caused by too much activity in the Hh pathway; colon cancer results from an overexpression of a different pathway, Wnt (Wingless N-terminal protein), Platika told HMS Beagle. Curis is developing antagonists for basal cell carcinoma and colon cancer, both in Phase I testing. Sporadic basal cell carcinoma is the most common form of skin cancer, and, while it is highly curable, surgery can disfigure patients, "so there is a pressing need for a better therapy," Platika says. CUR-61414 is a small molecule that is injected locally into a lesion; it seems to shut down the pathway and cause apoptosis.”

http://www.grg.org/Curis.htm


Also Roeland Nusse, Ph.D on the curis scientific board is a wnt specialist.


Any other thoughts?

Thanks HH

I see the connection that you are talking about regarding RNAi,Wnt and HH pathways. Is it safe to assume that in order to target many of the issues that Curis is working on they will need to involve RNAi,WNT and HH to be successful?

In your travels, have you noticed what Platika is currently working on or who he is working for since he left Curis? Also, in your opinion, what was the reason for the termination of the 2001 BCC trial?

Yes theoretically speaking RNAi would probably be the best way to target pathways. This is new technology and the delivery still needs to be perfected. IMO I think the current Hh antagonists will work really well based on the pathway mechanism. But again this pathway is relatively new and there is a lot that remains to be discovered. There is a lot of animal data that supports the current Hh antagonists.

Regarding your other question, Mr. Platika is no longer with curis. Not sure why, but i think it had to do with his business model. I’m also not sure why the BCC phase 1 trail was terminated. Maybe somebody else can help us out with the last couple of questions.

Now it is this

5:00 - 7:00 PM Drug Targets in the Wnt Signaling
Registered attendees to this meeting can view Abstracts for this session starting on 03/07/2006 Ballroom 2-3
Paul G. Polakis, Genentech Inc.
Therapeutic intervention in the wnt signaling pathway.

Xiaoyan Michelle Zhang, Curis, Inc
Short Talk: Identification of Small Molecule Antagonists of Wnt Signaling

article

The 11th has come and gone and no public release on curis and genentechs second collaboration.