Phase I trial of convection-enhanced delivery of IL13RA2 and EPHA2 receptor targeted cytotoxins in dogs with spontaneous intracranial gliomas Although only in dogs now, this is impressive results for a phase 1 dose finding trials. I have long been interested in this approach. About 15 years ago a phase 3 trial of CINTREDEKIN BESUDOTOX (IL13-PE38QQR) failed (although some patients did very well). The researchers analyzed the trial, figured out why it did not work and fixed it. The 2 main problems were the delivery by convection enhanced delivery was not good enough at that time - but it is now, and the receptor they chose was not restricted to only brain tumor. They changed from the wild type IL13 receptor to the mutant Il-13ra2 which is mostly found in tumors. They then added a second receptor, EPHA2 which is also only found in tumor. Unfortunately, it has been hard to get this into human trials because the first generation failed. Now with proof of concept in dogs, hopefully it will move to human trials quickly!
The dopamine receptor antagonist trifluoperazine prevents phenotype conversion and improves survival in mouse models of glioblastoma This article says that although radiation improves survival for glioblastomas, it also makes the tumor harder to treat. They found that by adding the drug trifluoperazine (which is approved for psychiatric disorders) at the time of radiation, they were able to preserve the benefit of radiation but stop the conversion that causes the tumor cells to be harder to treat. In mice, it resulted in longer survivals!
There is a different clinical trial now of another dopamine receptor antagonist, Onc-201, being tested for H3K27M mutant gliomas. They are testing it during and after radiation, as well as only after. Comparing the 2 may show the effect described in the article- hopefully longer survivals!
Prognostic Value of ABO Blood Groups in Patients with Glioblastoma Multiforme This is fascinating but needs to be confirmed in larger studies. For patients with Glioblastoma, they found median OS was 22 months in blood group O whereas 14 months in blood group A, 11 months in blood group B and 6 months in blood group AB. This could be significant when looking at clinical trial data. Blood type is usually not analyzed but it appears to make a larger difference in survival than any treatment ever tested.
This study shows how complicated the biology of these tumors are. You can not just say that because something makes sense and seems obvious, it should work. In theory, the ketogenic diet should slow down tumor growth. There are even a few small gbm studies that suggest it might help. This study shows the opposite - that it had the potential to make the tumor grow faster, at least in the test tube.
This is not proof one way or the other. More research needs to be done.
