"... most patients eventually develop Enz resistance that may involve inducing the androgen receptor (AR) splicing variant 7 (ARv7). Here we report that high expression of monoamine oxidase-A (MAO-A) is associated with positive ARv7 detection in CRPC patients following Enz treatment.
"Targeting MAO-A with phenelzine or clorgyline, the FDA-approved drugs for antidepression, resensitize the Enz resistant (EnzR) cells to Enz treatment and further suppress EnzR cell growth in vitro and in vivo."
Chlorgyline is available for research purposes according to Wikipedia - that leaves phenelzine, which has the following common side effects "... may include dizziness, blurry vision, dry mouth, headache, lethargy, sedation, somnolence, insomnia, anorexia, weight gain or loss, nausea and vomiting, diarrhea, constipation, urinary retention, mydriasis, muscle tremors, hyperthermia, sweating, hypertension or hypotension, orthostatic hypotension, paresthesia, hepatitis, and sexual dysfunction (consisting of loss of libido and anorgasmia). (Wikipedia) Manageable, I think.
Phenelzine can also cause B6 deficiency and foods like cured cheeses and meats would have to be avoided due to the presence of tyramine.
How often would one have to take phenelzine? It appears that phenelzine irreversibly inhibits/deactivates the MAO enzyme and the effect lasts for up to 2 weeks. Since the turnover of cellular components in PCa cells is high, it would probably have to be taken more often - a phase I trial is needed.
I presume that what applies to enzalutamide resistance with respect to AR-V7 also applies to abiraterone. I would think that phenelzine would slow progression with abiraterone as well.
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