RE:Question for the medical team In my view you can think of basically two sources of info for that list. One comes from the scientific literature, research groups discovering sortilin in different cancer. The other comes from THTX's own work confirming those findings. A lot of the previous discoveries in cancer are collated into various databases online of the 1000's of different cancer markers/receptors/targets.
There is a section in most of THTX's poster labelled as "microarray". These are commercially available products. They are essentially prepared microscope slides of various cancer and non-cancer tissues that you can use to look for sortilin in tissues. The other way THTX prove the presence of sortilin is by "western blot". Both work but in my view the microarray work is the most compelling. Thtx did some excellent microarray work in the two recent AACR posters. The detail in Ovarian was particularly impressive, the numbers they did and the way they broke down into the different types of ovarian cancer really caught my eye.
The way I think I would approach identifying all the different cancer types that might possess sortilin is to use the literature and databases to identify potential targets and then confirm this with your own microarray work. Some of the sortilin cancer papers are pretty compelling without confirmation. My guess would be the growing list is just the product of that process in action. So the longer list now is a product of all that microarray (and western blot) work they've been doing since acquiring the program, it got longer on the back of the most recent work. I guess it might get longer still.
I don't think any of this addresses the issue of heterogeneity directly. Just eyeballing the microarrays it does look like in most of the slides they show that there is a general increase in sortilin in the majority of cancer cells but there is also some areas more heavily stained and some cases where you can see very heavily stained individual cells. I think heterogeneity is ultimately going to be resolved empirically, basically how the human data looks. There are some ideas you can think about. The literature suggests sortilin plays a role in cancer cells, that role looks like it involves stemness, the transition from differentiated cells to stem-like cells. These cells have greater plasticity, a greater ability to adapt, become resistant, metastasize and are largely the source of heterogeneity. If they find the drug is targeting these cells that might be a good thing in taking out the deadliest cells. It's worth remembering all cancer drugs are going to potentially suffer from heterogeneic cells, it doesn't necessarily stop them from providing clinical benefits or getting approved.
SPCEO1 wrote: And I really would like to see JFM1330 still be on that team!
What do you take away from the ever increasing number of cancers TH-1902 is targetting? Is this simply a result of ongoing pre-clinical testing on different tumors to determine how much sortilin they are over-expressing? Have we reached the end of the additions to the list or could there be many more? What are the chances if TH-1902 works on one cancer overexpressing sortilin that it would work on all others too? I have to think it is more complicated than that. JFM1330 has previously noted the hetergeneosity of cancer tumors in humans versus the xenografts the pre-clinical work is done on. Could the sortilin factor be strong enough to overcomme the differences in tumors?