Tivatinib (ARQ-197)

[dita]

Thanks for posting Paul. Can you tell me a little more about it- is it a targeted therapy and does it work in combination with herceptin? Is the idea that it works on all types of bc or only her2?

[donocco]

Ill do some research on it. What i put down was very preliminary. I sent an article on the Hepatocyte Growth factor to my wife's computer at work and Ill read it tonight. Tivatinib or ARK-197 inhibits the Kinase enzyme in the receptor that the Hepatocyte Growth Factor attaches to. When I get a better understanding of the action of the Hepatocyte Growth Factor, Ill have a better understanding about Tivatinib. It seems the more you learn about something the more questions come up.

One of the names for the Hepatocyte Growth Factor is C-Met and Met stands for mesenchymal-to epidemal transformation. Cancer cells have to change shape before they start spreading. Once they change shape they become more motile and can spread. This is a guess about C-Met but I may be on track. If Im wrong Ill correct this.

To answer your question Diva its not just breast cancer or primarily breast cancer. In order for Tivatinib to be effective there apparently has to be an overactivity of the C-MET Tyrosine Kinase. This occurs in about 80% of Pancreatic cancers, I don't know what percentage of breast cancers, or if C-met is more active in, say, triple negative breast cancer, or Her2Neu positive breast cancer. Ill see what I can find.

Tivatinib seems to be an interesting drug. It must cross the blood brain barrier to be a preventitive against HER2positive brain mets. Ill post the information I can find. It seems to be worth spending some time with this drug.

Paul

[donocco]

I read the article on C-MET and learned a lot. I dont know if it would make sense putting it on the board. Its sort of an A-B-C-D-E-F thing, A being C-met which is connected to another protein (B) which is connected to another protein (D) which is conncected to all the other proteins and after F you get a reaction, be it increased cancer cell growth or increased cancer cell motility. To make it more complicated, protein B might stimulate Protein C1 and you have a different cascade that branches out. There are so many connections and interconnections and branches and subbranches, it can make your head spin. This is called signal transduction and is one of the reasons finding effective treatments for cancer is so complicated. If you block one pathway, a different one can take its place. Im still researching Tivatinib. The C-met (hepatocyte growth factor receptor is located in the cell membrane (like the Her-2 receptor) and the B,C,D,E F protein connections go deeper into the cell and eventually effect the cell nucleus.


Paul