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Advanced Prostate Cancer

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Has Anyone Heard that it’s More Common that Patients on Abiraterone (Zytiga) are more prone to their PC morphing into Neuroendocrine ?

Shorehousejam profile image
14 Replies

I read a post today that it’s more common that patients on Abiraterone (Zytiga) are more prone to their Prostate Cancer morphing into Neuroendocrine Carcinoma?

Is this true?

Any other Medications that are prone to have it Morp into Neuroendocrine Carcinoma ?

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Shorehousejam profile image
Shorehousejam
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mperloe profile image
mperloe

This study suggests that AA is not causative of this progression. pubmed.ncbi.nlm.nih.gov/288...

timotur profile image
timotur

This study says it's associated....

Emerging evidence suggests that NEPC develops as a transdifferentiation from prostate adenocarcinoma, in response to androgen deprivation therapy and/or treatment with inhibitors targeting AR signaling pathways (5). During NEPC development, cells lose their granular structure and demonstrate small cell neuroendocrine-like morphology, positive for typical neuroendocrine markers such as chromogranins, synaptophysin (SYP), and neurospecific enolase (NSE) but little or very low levels of AR and AR-regulated gene expression (6). Since AR signaling is required for epithelial cell differentiation during prostate development, inhibition of AR pathway likely initiates developmental reprogramming of prostate adenocarcinoma to neuroendocrine tumors through a transdifferentiation mechanism (7). Unlike prostate adenocarcinoma, neuroendocrine tumors are very aggressive with median cancer-specific survival is less than 2 years (8). Conventionally, neuroendocrine prostate cancers have been managed clinically with cisplatin-based chemotherapy regimens, however further identification and understanding of the oncogenic drivers of this phenotype necessitates the development of novel targeted therapies.

tcr.amegroups.org/article/v...

Shorehousejam profile image
Shorehousejam in reply totimotur

So, no matter what hormones, one is on Zytiga or Nubeqa it can morph?

timotur profile image
timotur in reply toShorehousejam

It appears so, but it's not 100% of the time. I remember a study by Aargawahl that said 20% of one study population had so-called "treatment-emergent" NEPC that had been taking AA.

tau.amegroups.org/article/v...

Shorehousejam profile image
Shorehousejam in reply totimotur

Unbelievable as if it’s not hard enough to survive, the meds can cause it…sickening

KocoPr profile image
KocoPr in reply toShorehousejam

without the meds you would survive as long.

edited I meant wouldn’t

PCaWarrior profile image
PCaWarrior in reply toKocoPr

FYI: BAT prevents the necessary AR changes. You go backwards but not forwards.

KocoPr profile image
KocoPr in reply toPCaWarrior

Your preaching to the choir buddy

KocoPr profile image
KocoPr in reply totimotur

That article was written in 2016 before Nubeqa was approved in 2019 so Nubeqa is not part of your assumption.

Nubeqa has a completely different structure than all the other ARi

Tall_Allen profile image
Tall_Allen

No. Whoever wrote that didn't understand that the chances of treatment-emergent NE increases after any treatment. Kill off enough cancer cells and what's likely to be left over is impervious to whatever you've used to treat it. That might be NE or it might be something worse.

KocoPr profile image
KocoPr in reply toTall_Allen

Exactly right! The androgen independent cells will take advantage of a non competitive environment and start multiplying and using different available pathways and or mutate as in NEC.

That is why i am doing BAT, in order to keep the beast fed intermittently but caged in the hopes that the beast is content to stay in its cage.

Tall_Allen profile image
Tall_Allen in reply toKocoPr

I hope it works for you, and that you are doing it as part of a clinical trial. So far, it has only been advantageous in men with certain androgen receptor characteristics.

KocoPr profile image
KocoPr in reply toTall_Allen

I certainly hope it works also! Not part of clinical trial as i am HSPC. I don’t like the idea of but understand the rigidity of clinical trials but i am adjusting my cycles per my PSA responses. That can’t be done in the present BAT trial formats. My OC at MGH is monitoring me, plus data is going to Denmeade at JOHNS HOPKINS.

j-o-h-n profile image
j-o-h-n

Worse? Like when your electric car needs a charge on the Long Island Expressway...

Good Luck, Good Health and Good Humor.

j-o-h-n Saturday 09/02/2023 2:55 PM DST

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