Will Prozac help combat brain cancer? If the answer to that question is yes, exciting opportunities will await victims. As other cancer research has done.
Research on Glioblastoma: Will Prozac Help Combat Brain Cancer?
It seems amazing that a decades-old antidepressant could help with glioblastoma. Yet, consider the following research.
The highly lethal brain cancer glioblastoma (GBM) poses a daunting challenge. Because the blood-brain barrier renders potentially druggable amplified or mutated oncoproteins relatively inaccessible. Here, we identify sphingomyelin phosphodiesterase 1 (SMPD1). It is an enzyme that regulates the conversion of sphingomyelin to ceramide. As an actionable drug target in GBM.
We show that the highly brain-penetrant antidepressant fluoxetine [more often known as Prozac] potently inhibits SMPD1 activity. By killing GBMs, through inhibition of epidermal growth factor receptor (EGFR) signaling. And via activation of lysosomal stress. Combining fluoxetine with temozolomide, a standard of care for GBM, causes massive increases in GBM cell death. That resulted in complete tumor regression in mice. Incorporation of real-world evidence from electronic medical records in insurance databases is positive. Because this evidence significantly increased survival in GBM patients treated with fluoxetine. Not seen in patients treated with other selective serotonin reuptake inhibitor (SSRI) antidepressants. These results nominate the repurposing of fluoxetine as a potentially safe and promising therapy for patients with GBM. And suggest prospective randomized clinical trials.
In addition, our paper provides new and unique insight into the critical dependency of GBMs on SMPD1. And its impact on plasma membrane dynamics. Including EGFR signaling. We find a critical link between sphingomyelin metabolism and oncogenic receptor signaling on the plasma membrane of GBM cells. Lipids function as essential components of the plasma membrane. And their compositions are precisely regulated in forming signal microdomains.
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