RE:RE:RE:RE:RE:Sortilin infoYou're right --It is a complex issue and does seem highly novel as we keep learning about it with them. It is likely why the investigators were perfectly happy to drop down to the 300mg level as they probably surmised (or saw) it was enough to have a strong therapeutic effect, but not enough to cause serious issues with the sortilin not in the cancer cells. Marsolais and Belevieu have said numerous times that there's not a lot of sortilin expression in normal tissue compared to cancerous. How they quantify that other than the staining, I don't know. You are also right that what I meant by damaged cells was cancerous cells.
I guess my question would be is sortilin1, as a traget, any different than any other target used for an ADC or PDC? It seems many of the others (Nectin, Trop2, etc...) may not show as strong a relationship between severity and expression, but I'm just guessing from some of the statements Belevieu made. I guess what you're looking for the is difference between normal expression and high expression and the greater that difference, the more effective a targeting treatment can be. In other words, a target that at refractory levels of cancer is 6x more than normal would be a better target to use than one that is only 2x higher. Differences are important I think.
By the way, that paper I found isn't that helpful because it's talking about how unregulated hypertension is correlated with soluable sortilin in blood.
jfm1330 wrote: About the 90/10 sortilin distribution, I was aking the question to know if the ratio is the same in cancer cells, or in cancer cells at different stages of cancer evolution. I am not sure they have a straightforward way to test for that. Maybe some studies can give a rule of thumb to apply to healthy cells, early cancer cells and advanced cancer cells. By the way, damaged cells and cancer cells are they the same for you or are talking about two different things. A cell can be damaged and not cancerous. One thing is sure, is that the more we scratch, the more complex this sortilin thing is. Remember that sortilin on the cell membrane can also be cleaved to release what they call soluble sortilin.
Wino115 wrote: For JFM to clarify the data I mentioned, it was that in a normal healthy cell only 10% was on the cell surface and 90% within the cell. That helped with the fact that off-tumor take-up would be fairly low. The paper then stated non-healthy tumor cells see far more go to the surface and the worse off the tumor, the more gets sent to the surface. They postulated why a damaged cell sent more to the surface. I will go dig out the paper again as it is a brand new one written by a new group of scientists.
I think this is scientific benefit of Sortilin as a target, not the opposite as you are surmising. Healthy tissue does not send it to the surface so gets much less chemo internalized, but tumor cells send a whole lot to the surface and recycle it constantly back to the surface. The difference between healthy and tumor was very large. Also, one of the breast cancer studies had something like 500 plus samples they had taken over the years of healthy and tumor tissue from live humans and they also found the large Sortilin expression difference.