Iron Induces Cell Death and Strengthens the Efficacy of Antiandrogen Therapy in Prostate Cancer Models, Cinical Cancer Research, 2020 Dec 1

[cujoe]

The following paper from 2020 might be of interest to those using the antiandrogen bicalutimide as a major component in their treatment programs. Much has been made of cancer cell death by ferroptosis and from this first paper it seems probable that there is some potential synergy between iron supplementation and bicalutamide. (Also linked is a more recent Nature review paper on ferroptosis in PCa):

The following passage is from the Discussion Section from the first paper:

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Our results suggest that tumors with active androgen signaling might be intrinsically iron sensitive. We speculate that this would also be relevant for castration-resistant tumors where AR signaling is active, such as tumors characterized by abnormal AR overexpression or constitutively active mutated AR. Importantly, our results also show that castration-resistant tumors with inactive or absent androgen signaling pathway, like those lacking AR and/or characterized by neuroendocrine differentiation might be converted into iron sensitive by combining iron with antiandrogens.

Bicalutamide enhances the oxidative circuit initiated by iron

All prostate cancer cells proliferate less when exposed to bicalutamide–iron combination than when exposed to each single treatment. This effect is particularly evident in PC-3 cells, whose proliferation is barely impaired in vitro and unaffected in vivo by iron or bicalutamide alone. Although AR signaling is nonfunctional in PC-3 cells, high-dose bicalutamide mildly reduces PC-3 viability, suggesting that the androgen inhibitor has off-target effects that might intersect oxidative iron homeostasis, indirectly increasing iron toxicity. (emphasis added)

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Links to both papers are below:

Iron Induces Cell Death and Strengthens the Efficacy of Antiandrogen Therapy in Prostate Cancer Models, Cinical Cancer Research, 2020 Dec 1;26(23):6387-6398. Epub 2020 Sep 14.

aacrjournals.org/clincancer...

The role of ferroptosis in prostate cancer: a novel therapeutic strategy, Nature, Prostate Cancer and Prostatic Diseases, Review Article, Published: 02 September 2022.

nature.com/articles/s41391-...

Maybe us bical users need to also become Ironmen?

Stay S&W, Ciao - cujoe