tag:blogger.com,1999:blog-6235733697979948062.post5361884827837346916..comments2024-03-19T00:33:30.191-07:00Comments on our brain tumor cocktails and stories: VXM01 (VEGFR-2 DNA Vaccine) trial ? Stephen Whttp://www.blogger.com/profile/00777652648990108253noreply@blogger.comBlogger4125tag:blogger.com,1999:blog-6235733697979948062.post-22757754542250952592017-08-01T03:02:13.133-07:002017-08-01T03:02:13.133-07:00Hello Matjaz!
Toca 511 + Toca FC is something I h...Hello Matjaz!<br /><br />Toca 511 + Toca FC is something I hope will succeed and get FDA (+ EU) approval fast.<br /><br />To my understanding the trial is not currently recruiting:<br />https://clinicaltrials.gov/ct2/show/NCT02414165<br /><br />thanks anyway!<br /><br />br,<br />JuhaJuhaHhttps://www.blogger.com/profile/10532555954954439072noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-24338168424627531932017-07-31T23:31:03.572-07:002017-07-31T23:31:03.572-07:00Hey guys,
how about that Toca trial, which showed ...Hey guys,<br />how about that Toca trial, which showed some good results on IDH1mut?<br /><br />Take care!Matjazhttps://www.blogger.com/profile/03958991504875518577noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-63215512707574297522017-07-30T23:42:25.211-07:002017-07-30T23:42:25.211-07:00Thanks Stephen!
We'll meet my sister's ne...Thanks Stephen!<br /><br />We'll meet my sister's neurosurgeon in couple of weeks and we'll discuss with oncologist again after that. I'll let you know how it goes.<br /><br />br,<br />JuhaJuhaHhttps://www.blogger.com/profile/10532555954954439072noreply@blogger.comtag:blogger.com,1999:blog-6235733697979948062.post-9300548132615307182017-07-30T07:54:24.146-07:002017-07-30T07:54:24.146-07:00Looking at mRNA data, G-CIMP positive gliomas (rea...Looking at mRNA data, G-CIMP positive gliomas (read IDH1 mutant) have a greatly reduced expression of VEGF-A and greatly increased expression of VEGF-B versus non-GCIMP gliomas (mostly GBM). The receptor VEGFR1 (gene name FLT1) is a receptor for VEGF-A as well as VEGF-B. The receptor VEGFR2 (gene name KDR) that this vaccine is targeting, is a receptor for VEGF-A, but not VEGF-B.<br /><br />Based on this data, I would expect this vaccine to be less effective for IDH1-mutant gliomas compared to IDH wild-type GBM, and that the VEGF-B/VEGFR1 signaling axis might be a better target for IDH1-mutant gliomas. In support of one half of this conclusion, Avastin, which is an antibody against VEGF-A, has a poor track record for low grade gliomas (the majority of which are IDH1-mutant) and in the TAVAREC clinical trial, Avastin did not improve progression-free survival nor overall survival for grade 2 and 3 astrocytoma patients.<br /><br />Again in terms of mRNA expression, PDGFRA is the most highly expressed receptor tyrosine kinase in G-CIMP positive gliomas, whereas EGFR is more highly expressed in non-G-CIMP (IDH non-mutant) glioblastoma.<br /><br />I would go with the TMZ + olaparib (+ disulfiram/copper + long-chain omega 3 fish oils). <br /><br />Alternatively, if I were pursuing immunotherapy for IDHmutant glioma I would attempt to combine it with one of the mutant IDH1 inhibitor drugs (if I could get it on compassionate use). The reason being that 2-hydroxyglutarate (produced by mutant IDH1) causes immunosuppression in the tumor environment.<br /><br />I would not combine mutant IDH1 inhibitors with the TMZ + olaparib cytotoxic strategy, as 2-hydroxyglutarate sensitizes the tumor to many of these cytotoxic therapies, and is one of the reasons mutant IDH1 gliomas have a better prognosis and are more responsive to conventional therapies.Stephen Whttps://www.blogger.com/profile/00777652648990108253noreply@blogger.com