A newly published case study describes the case of a 57-year old GBM patient, with poor prognosis due to a KPS of only 50 and postoperative neurologic symptoms. The patient was being treated for schizophrenia at the time of GBM diagnosis with risperidone at a dose of 6-6.5 mg per day. He ended up going 5.5 years without recurrence, and then lived for an additional year after first recurrence. This paper posits a possible correlation of his unexpected progression-free survival with his use of risperidone.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5066542/
In 2010, Richard Kast published a paper hypothesizing that risperidone, pimozide, and paliperidone could be useful for GBM treatment as 5-HT7 serotonin receptor antagonists.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2990148/
Additionally, risperidone is a potent inhibitor of D2 and D3 dopamine receptors. D2 has been described as a valid target for GBM therapy:
https://www.ncbi.nlm.nih.gov/pubmed/24658464
Finally, a more recent paper by Richard Kast and Marc Halatsch proposing D3 dopamine receptor as a target for GBM therapy.
https://www.ncbi.nlm.nih.gov/pubmed/24242756
Very interesting. What else I find interesting is the individual had wild-type IDH1 which can possibly indicate a proneural GBM subtype. What I find interesting about that is that in the recent study "Drug repurposing for glioblastoma based on molecular subtypes" by Yang Chen & Rong Xu their algorithm predicted that antipsychotics and antidepressants would work best in proneural subtypes.
ReplyDeleteSee pic below:
http://imgur.com/a/ormqR
It's certainly possible that this GBM could have fallen into the proneural category. However IDH-mutant GBM is usually proneural, while IDH wild-type GBM is more spread out into classical and mesenchymal subtypes as well as proneural.
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