http://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1409926?needAccess=true
Some of the data contained in this study was used as justification for the CHLOROBRAIN trial
https://clinicaltrials.gov/ct2/show/NCT02378532
Tuesday 30 January 2018
Chloroquine for GBM with EGFRvIII mutation
EGFRvIII expression triggers a metabolic dependency and therapeutic vulnerability sensitive to autophagy inhibition
http://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1409926?needAccess=true
Some of the data contained in this study was used as justification for the CHLOROBRAIN trial
https://clinicaltrials.gov/ct2/show/NCT02378532
http://www.tandfonline.com/doi/pdf/10.1080/15548627.2017.1409926?needAccess=true
Some of the data contained in this study was used as justification for the CHLOROBRAIN trial
https://clinicaltrials.gov/ct2/show/NCT02378532
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"...we retrospectively
ReplyDeleteanalyzed 43 GBM patients that were included in a randomized,
placebo-controlled phase II trial. Of the analyzed
patients, 28 patients received CQ in combination with carmustine
and radiotherapy. EGFRvIII expression was assessed
immunohistochemically and observed in 22 of 43 (51%)
patients...
Although the number of analyzed patients is low, these
results are encouraging as CQ treatment improved median
survival from 5 to 10 mo in patients with EGFRvIII-negative
GBM (Fig. 6C, p = 0.0002). Strikingly, median survival of
patients with EGFRvIII-positive GBM increased from 3 to 15
mo (p = 0.0006), confirming our pre-clinical findings and
the therapeutic potential of CQ in the treatment of EGFRvIII-expressing
tumors."
Stephen, I recall discussing other studies that pointed to the effectiveness of Chloroquine in the case of EGFRvIII about 3 years ago now. Seems there is some pretty solid evidence for CQ with EGFRvIII tumors. Thank you for continuing to bring important studies to our attention!
ReplyDeleteYes, this recent publication is showing the same clinical data that we were discussing several years ago. At that time it was unpublished, and finally it has been published.
Delete1. As is now known, tumors with a mutation EGFRvIII use autophagy more for survival under stress, such as hypoxia and fasting and chloroquine is more effective in case of such a mutation.
ReplyDeleteHowever, then what kind of survival method does the tumor use without EGFRvIII mutation?
2. In this new study, chloroquine is proposed to be combined with calcium-mobilizing compounds.
https://www.ncbi.nlm.nih.gov/pubmed/29902340
Unfortunately, the full version of the study is not yet available through http://sci-hub.tw/
It is interesting which calcium-mobilizing compounds can be used?
Autophagy is a mechanism used by all cells to promote survival under stress. It's just that EGFR+ tumor cells seem especially reliant on it.
DeleteIt's strange the article is "open access", yet there's no link given for the full PDF download.
https://onlinelibrary.wiley.com/doi/10.1111/cas.13695
In any event, the abstract makes it sound like nigericin is the calcium mobilizing compound.
"Nigericin in combination with ATG5 deficiency synergistically suppressed spheroid formation by glioma cells in a manner mitigated by Ca2+ chelation or CaMKK inhibition, indicating that in combination with autophagy inhibition, calcium-mobilizing compounds contribute to efficient anti-cancer therapeutics."
You can download the "supporting information", but not the study itself. I think this is an error by the journal to not provide a link to the PDF of the study.
Deletehttps://onlinelibrary.wiley.com/action/downloadSupplement?doi=10.1111%2Fcas.13695&attachmentId=2218747904