HER2 Support Group Forums - View Single Post - Happy New Year--a new and promising oral drug which crosses the blood brain barrier

Lani · 12-31-2007, 09:48 AM

what is different is that this TKI is much more specific

Most TKIs are promiscuous (yes, that is the word I have learned to use by reading the articles and listening to conference talks!) in that they act not just on one kind of receptor's phosphorylation site, but that of any of a number of similar receptor's phyosphorylation site (to block their function)

Thus lapatinib may work on IGFR1 as well as EGFR and her2, some VEGF inhibitors may also work on PGFR.

The problem with that is that they can have unanticipated negative functions as well as beneficial functions, as these receptors are found on all sorts of cells and can have important functions necessary to those people taking them.

The second difference is that it blocks not just her1 and 2 like lapatinib, but her4 as well (her 3 has no functional intracellular phosphylation site and has to pair with her1,2,or 4 to "borrow" theirs) do this drug may essentially do the same as that article on "curing" mice with the 3 drug combo--herceptin, pertuzumab and iressa. And this drug is oral, not IV (pertuzumab is IV, iressa a pill). Since iressa is made by a different drug company than herceptin and pertuzumab I think it will be a long time before that combo is tested in a clinical trial, unless Genentech can substitute Tarceva for Iressa.

This is one drug made by one company (with a lot of money from Sales of baby powder and baby shampoo as long as our population keeps growing!)
THAT BRINGS HOPE trials will proceed faster than if they had to test a three drug combination, with only one of the drugs being FDA approved already.

So the answer to "what's the big deal" is ...it MAY turn out to be a big deal!

Happy New Year!

12-31-2007, 09:48 AM	#5
Lani Senior Member Join Date: Mar 2006 Posts: 4,778	fullof beans what is different is that this TKI is much more specific Most TKIs are promiscuous (yes, that is the word I have learned to use by reading the articles and listening to conference talks!) in that they act not just on one kind of receptor's phosphorylation site, but that of any of a number of similar receptor's phyosphorylation site (to block their function) Thus lapatinib may work on IGFR1 as well as EGFR and her2, some VEGF inhibitors may also work on PGFR. The problem with that is that they can have unanticipated negative functions as well as beneficial functions, as these receptors are found on all sorts of cells and can have important functions necessary to those people taking them. The second difference is that it blocks not just her1 and 2 like lapatinib, but her4 as well (her 3 has no functional intracellular phosphylation site and has to pair with her1,2,or 4 to "borrow" theirs) do this drug may essentially do the same as that article on "curing" mice with the 3 drug combo--herceptin, pertuzumab and iressa. And this drug is oral, not IV (pertuzumab is IV, iressa a pill). Since iressa is made by a different drug company than herceptin and pertuzumab I think it will be a long time before that combo is tested in a clinical trial, unless Genentech can substitute Tarceva for Iressa. This is one drug made by one company (with a lot of money from Sales of baby powder and baby shampoo as long as our population keeps growing!) THAT BRINGS HOPE trials will proceed faster than if they had to test a three drug combination, with only one of the drugs being FDA approved already. So the answer to "what's the big deal" is ...it MAY turn out to be a big deal! Happy New Year!