jfm1330 wrote: I am unable to find a website for Sortina Pharma. That being said searching with some key words I found some interesting scientific articles. I found the following about the role of sortilin in breast cancer:
Interestingly, sortilin has been associated with metastatic potential in breast cancer [17] and is highly expressed in breast cancer cell lines compared to non-tumorigenic breast epithelial cells [17]. In addition, siRNA knockdown of sortilin inhibited breast cancer cell adhesion, migration and invasion suggesting that sortilin indeed is involved in breast cancer progression https://breast-cancer-research.biomedcentral.com/articles/10.1186/s13058-018-1060-5
So if you elimiate the expression of sortilin with siRNA, you end up suppressing signs of cancer aggressivity. What needs to be understood is that by eliminating sortilin from the cancer cell membrane, you eliminate the receptor for progranulin, so you deregulate the axis sortilin-progranulin. But when you think about it, a sufficient enough dose of TH1902 is doing somenthing similar to siRNA. TH1902 by saturating sortilin ends up having it out of the cell membrane and all internalized inside the cell. So TH1902, like siRNA, is also messing up the sortilin-progranulin axis involved in cancer aggressivity. So all that is probably linked to the inhibition of the vasculomimicry process that is involved in cancer aggressivity.
From the little I have been able to find, Sortina approach is to block sortilin capacity to bind progranulin with a small molecule, and that would also be a way to mess up the sortilin-progranulin axis. This would be in line with my suggestion to use TH19P01 alone as anti-cancer agent complementary to PDCs based on it. But for that to work you would need a long acting release formulation like the one that exists for octreotide (Sandostatin LAR) in the treatment of neuroendocrine tumors, or a more stable analog of TH19P01. In this case the peptide octreotide (analog of the natural peptide somatostatin), is also the peptidic part of the PDC Lu177-Dotatate (Lutathera). So to treat neuroendorine cancers, they use octreotide LAR for chronic treatment, and the PDC based on octreotide (Lu177-Dotatate) for acute treatment. A similar thing, in theory, would be possible with TH19P01 and PDCs based on TH19P01, like TH1902 or TH2101.
I am talking about this just because it seems clear to me that sortilin could be used in different ways to fight cancer, and a similar combo therapy already exist to treat neuroendocrine tumors, with Sandostatin LAR and Lutathera. I know it's still a bit science fiction at the moment, but not totally. The path is clear, it just needs to be explored. But if TH1902, Thera will be able to gather the necessary ressouces to explore many possibilities related to sortilin.
Wino115 wrote: If we get POC, the hard part will be ranking which approach to do next, and then next, and then next!
On the CSC and Sortilin question, I recall that the Univ of Gothenburg team and their spinoff venture (Sortina Pharma) is studying the Sortilin/stem cell nexus for their mTNBC drug they hope to figure out. Their website or Univ research may have more on it.