RE:RE:Sortilin 1 Promotes Hepatocellular Carcinoma I don't know the answers but a few thoughts spring to mind from your post.
I don't ever remember reading about "reversing" cancer from a high stage to a low stage so I don't think that's a useful way to think about it.
When it comes to late stage solid tumour it seems quite common that drugs are getting approval with not so many Complete Responses.. quite often it's PRs that make up the majority of the ORR and this is backed up by some extended SD patients that contribute to the PFS number. So you can be looking for a lot less than the killing of every cancer cell in a person for the drug to be considered useful and valuable. I think we should be judging the drug by the standards other drugs are judged. It would be nice for the drug to produce some perfect outcomes but that's not what it is likely going to be judged on.
I'm sure there is a vast amount of variability in patients with cancer. You can imagine some patients where the new metastatic tumours are being seeded by a fairly homogenous line of cells. If they all express Sortilin then there's an opportunity to get a CR or something close, that might be where a small number of CRs come from. There will be many more patients where their tumours are much more heterogenous and the response is therefore ore mixed. I think once you have many tumours in a patient the expectations might be much lower than "cure". So clearing up some lung tumours that are causing COPD or emphysema might be the immediate goal or dealing with other such health issues.
It might be worth looking at the Complete Response rates from Trodelvy/Enhurtu to give some perspective on how much of an issue this is.
I think ultimately, like many things, the answer to these questions emerge as they record the experience of more and more patients on the drug.
Just as a separate idea. You can often look at an individual drug and think that maybe the benefits it offers are pretty limited. I think an alternative way to look at this is if you for example take the experience of breast cancer over the past fifty years. The survival rate is hugely improved. That hasn't all come from one drug, it comes from step improvements in diagnosis, drugs, the ability to combo drugs and the ability to provide multiple different types of intervention. If TH1902 gets an approval it becomes part of an armoury available to doctors (hopefully one of the more powerful weapons), it doesn't necessarily have to do all the lifting.
Wino115 wrote: This is a July 2022 article from a lab in China. I guess they're essentially showing what others have presented on the correlation between high sortilin expression and survivability --the worse the cancer, the higher the sortilin expression and the lower your probability of survival. So far, THTX has not mentioned liver cancer as one in the basket trial and I don't recall it being one in the original KOL presentation material from a few years ago mentioned as a high sort1 target to go after.
As I was looking through the charts on this, it did bring up a question in my mind that maybe the more science-oriented posters can offer a thought or two on. And that is, if TH1902 works due to the overexpression of sort1 typically seen in late stage solid tumor cancers, as it works to lower the tumor burden and cancer spread, does this reversion also lower the expression? In other words, if I take a stage 4/5 cancer and effectively reverse it back down to a stage 2/1 or less, won't that effect the efficacy of TH1902 going forward?
I suppose that's the problem with many cancer drugs and perhaps why there can still be many side effects as they improve. But for one that whose target is correlated with the severity of the disease, I guess there's a tipping point in which it's effectiveness is lessened. The pre-clinical didn't show that and maybe it's all about getting as much in the tumor to do it's thing as you can in the early stage and then you can modulate it lower if you need to. Anyway, a question for the scientists.
https://pubmed.ncbi.nlm.nih.gov/35847356/
Joemare wrote: Sortilin 1 Promotes Hepatocellular Carcinoma Cell Proliferation and Migration by Regulating Immune Cell Infiltration . 2022 Jul 8;2022:6509028. doi: 10.1155/2022/650902