RE:RE:Complexity of sortilin Rhost is one of the Univ of Gothenburg researchers who are the other sortilin focused group. They are solely focusing on TNBC and using sort1 to degrade cancer stem cells. She is now the CEO of the early stage Venture cap company they started and we've peaked at.
FYI, I did an extensive search 4 months ago to see if I could find anything on quantitatively derived genetic expressions for the popular cancer ADCs and found nothing. There are many papers that are similar to our sortilin ones showing staining in healthy and cancerous tissue and using the same low, mid, high, very high scale. So if Anyone can get beyond that it would be a breakthrough for our understanding of the ADC targets.
jeffm34 wrote: There is a short mention about cancer in the article.
Several groups have used AF38469 in biological experiments. As previously discussed, Rhost et al. discovered that sortilin-mediated endocytosis of progranulin is required for progranulin to induce metastasis of breast cancer cells. Delivery of AF38469 into MDA-MB-231 human breast cancer cell-xenografted mice via their drinking water during tumor growth completely inhibited progranulin-induced metastasis of the breast cancer cells into the lung (212). Yang et al. demonstrated that sortilin promotes glioblastoma invasion and treatment with AF38469 attenuated the migration of glioblastoma cell lines and decreased glioblastoma tumor growth and invasive capacity in mice (217). In addition, the survival time of the mice treated with AF38469 was significantly longer than that of mice in the control group (28.5 versus 18.5 days). Therefore, inhibition of ligand binding to sortilin with AF38469 may be a potential therapy for several cancers.
jfm1330 wrote: If you want to freak out about how complex the sortilin role can be, and how it can change from cell types, and even within the same cell type, read this very recent article published this year. Sortiln has over 50 possible ligands, and depending on the ligand, then the pathway within the cell can vary. Reading this article, it seems pretty clear that all sortilin expression is not the same and does not behave in the same way. In the context of TH1902, the big question that comes to mind is how sortilin in cancer cells compare to sortilin in healthy cells, and as I said, in healthy cells, the behavior of sortilin, so can it also vary from in cancer cells from on cancer type to another, and even within a cancer type depending on how advanced the cancer is. For example, is it the same in metastatic cancer as in non metastatic cancer? This article does not talk about cancer, it is focused on sortilin role in metabolism, but it is interesting to have an understanding of how complex the role of this receptor is. In the context of the recent press release about the grant to better understand the fate of TH1902 in TNBC, you can see that it will be a big task just to understand some aspect of it.
https://www.sciencedirect.com/science/article/pii/S0022227522000761