RE:RE:RE:RE:RE:RE:RE:RE:Not sure what's new? My thinking is: if you remove the cd133 data, then there's nothing to establish the activity is linked to cancer.
Even if "MMP9 a common marker for VM", maybe it isn't entirely specific, so the observation that CD133 (commonly asociated to Cancer Stem Cell activity) is upregulated does add some degree of confirmation that cancer-related VM is indeed in play?
qwerty22 wrote:
I also don't see the relevance of the cd331 point, that just seems to be a separate observation unconnected to the MOA they are describing here. If that has some relevance I'm missing then maybe things become more clear
qwerty22 wrote:
The full poster is available if you register for free for the conference. It comes with a short commentary from Christian.
In the commentary Christian does suggest that silencing of the Sortillin receptor (SR) does inhibit VM suggesting a specific role for SR in their formation. He also says that the drug-peptide conjugate shows it's effect at nmol and pmol concentrations. He doesn't specifically say that it is the inhibition of the SR that is leading to the VM inhibition.
But the poster is suggesting a dual action for the drug. In the conclusion they have a little schematic where the suggestion is the drug-peptide conjugate works by two separate mechanisms VM inhibition and cytotoxic cell growth inhibition. And the conclusion bullet points are certainly suggesting this. Personal I don't see where in the poster they have ruled out just the delivery of cytotoxic drug as the mechanism for also inhibiting the VM, maybe it's based on these very low inhibitory concentrations.
There is an option to ask the authors a question about the poster so I've specifically asked for clarification on that point.
You are right though a second MOA for the drug conjugate would be something novel and exciting.
jfm1330 wrote: Not sure about this affirmation. My understanding of this technolgy always was that the peptide carrier with high affinity to the Sortilin receptor was able to selectively bring a cytotoxic drug into cancer cells with minimal impact on other types of cells in the body. Now this sentence states that the peptide by itself would silence the role of Sortilin receptors in the vasculogenic mimickery (VM) process. If it's the case it would change the whole ball game, because if so, you would have a double anti-cancer effect, one from the introduction of a cytotoxic drug into the cancer cell, but also another effect from the peptide itself inhibiting the VM process of the tumor by interacting with the Sortilin receptors on the membrane of the cells. So it would be a double effect. Is it really the case or the IR person was just overoptimistic.
SPCEO1 wrote: - Our new data demonstrate that sortilin is a key player in the formation of VM structure - silencing sortilin stops the formation of the VM structure for both ovarian and TNBC cancer cells.