RE:RE:RE:RE:RE:RE:RE:Trodelvy's most direct competitor in TNBC Ph 1 data released I think the individual studies is the scientific literature are fairly good guides but eventually this needs to be proved empirically. I had a go at comparing trop1 to SORT1, got a little way through the process with a general conclusion that they were comparable but quickly gave up because the more I looked the less I liked my ability to draw meaningful conclusions. IHC just doesn't lend itself to comparing between studies all that well. That probably means thtx are going to need to look at what they get in their enrolled patients and match that to responses. That's really the only way to prove this out. If they show a relationship in this first program then you might project that relationship onto what is known about other cancers and begin to extrapolate from there.
I wouldn't go down JFM's route of trying to draw too many conclusions from the levels of staining at this point. Immuno-staining tissue samples is not really a quantative tool. Making the call that differences in the level of staining represent "huge" differences in the level of Sortilin is just an incorrect way to interpret this. It's too complex to explain but you could start by reading the "limitations" section in this paper.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2832341/
All things being equal a heavily stained sample PROBABLY has more Sortilin than a lightly stained sample, producing a test the can accurately quantify the difference is challenging (near impossible). But often all things aren't equal and often it's difficult to know if all things are equal or not. IHC is certainly a good research tool. You can probably make broad stroke conclusions using it but it always needs to be heavily caveated.
thtx are doing the right things, it's just I'm not fine with wild extrapolation from others.
Wino115 wrote: Interesting stains. I toyed around with this too, getting nowhere. But one thing that seemed to be true as I compared other targets is that it appears sortilin is in fairly low levels normally and has some concentration in the brain and a few other organs. It doesn't appear to be in concentration in many places in the body.
Secondly, it seems the differential becomes extremely large around the tumor environment, especially in those advanced cases they are targeting. This may help it stay fairly "on target" and have fewer side effects. But I can't say I know how either of those compares to other targets used. It may be similar, it may be uniquely good for the purpose. My guess is those traits are no worse than any others being used for solid tumors, and for the advanced cases where the unmet need is, it may be better given the large overexpression the tumor environment causes. But I'm ok just thinking it's similar to others at worst, until someone can be more definitive around it.
jfm1330 wrote: One thing Thera did not explain, and I made some research about that on the net to find some answers, is how sortilin expression compare to other receptors expression that are targets for other PDCs and ADCs. I did not find any data where you would be able to compare the levels of receptors expression.The only thing I found is a visual comparison from histological staining of sortilin expression in breast cancers from two levels of low expression (1 and 2) and two levels of high expression (3 and 4). One thing is sure, just within the possible sortilin expression levels, the differences of expression are huge. If you have level 4 of sortilin expression, it is hard to imagine how TH1902 would not be much more efficacious, if you put aside other possible factors like docetaxel resistance.
https://bmccancer.biomedcentral.com/articles/10.1186/s12885-021-07854-0/figures/1