About ATR Inhibitors… I Have a Tier 1... - Advanced Prostate...

Advanced Prostate Cancer

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About ATR Inhibitors… I Have a Tier 1 ATM Frameshift Mutation is response better than Keytruda perhaps?

Shorehousejam profile image
22 Replies

Started Chemotherapy yesterday

with Cabazitoxel

And Carboplatin

For Liver Mets & Lung Nodules

I have to have pathology on tissue done for second opinion as I’m not sure if they did a complete staining histology

It Thankfully came back as pca Adenocarcinoma

Still believe it seeded the liver lesions / mets and lung nodules from growing tumor on prostate bed, that I never radiated…see bio

Anyone know anything about the best parp inhibitors that I may successfully respond too or ATK inhibitors?

Information:

Taken together, these data suggest that ATM loss is a potential biomarker for ATR inhibitor sensitivity in prostate cancer and that ATR inhibition may be a more promising therapeutic strategy than PARP inhibition for the subset of prostate cancer patients with tumor ATM loss.”

ncbi.nlm.nih.gov/pmc/articl....

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Shorehousejam profile image
Shorehousejam
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22 Replies
Tall_Allen profile image
Tall_Allen

Unfounded belief about spread. You don't seem to understand that cancer growing into prostate bed are not mostly metastases, and that the cancer must be metastatic to spread. I don't see how such fantasies help you, but believe whatever gets you through the day.

You are looking at outmoded data. The ATR inhibitor clinical trial was terminated early because of no benefit.

PARP inhibitors don't work on ATM mutations.

Shorehousejam profile image
Shorehousejam in reply to Tall_Allen

MSK wants to give me Keytruda that’s why I’m looking at other options

Do you have anything to suggest?

Tall_Allen profile image
Tall_Allen in reply to Shorehousejam

Have you had Provenge?

Shorehousejam profile image
Shorehousejam in reply to Tall_Allen

No

Tall_Allen profile image
Tall_Allen in reply to Shorehousejam

During chemo is a good time to use it. It amps up the immune response, which would be otherwise depleted by chemo. Also, chemo makes more cancer antigens available to dendritic cells, so Provenge may work better. They may work synergistically.

Shorehousejam profile image
Shorehousejam in reply to Tall_Allen

Thank you

We requested a zoom call with MSK.

So asked about Provenge

Why do you think he wanting to do Keytruda and they are so many

Other parp inhibitors?

Tall_Allen profile image
Tall_Allen in reply to Shorehousejam

None of the PARP inhibitors work with ATM mutations, even if they are approved, and they are all quite toxic.

I have no idea why he wanted to do Keytruda- ask him.

Shorehousejam profile image
Shorehousejam in reply to Tall_Allen

Prostate cancer (C61) DIAGNOSIS:

A. Liver, lesion, biopsy: Small focus of metastatic prostatic adenocarcinoma; see note.

Note: The biopsy shows hepatic parenchyma with a small focus of adenocarcinoma that stains positive with a NKX3.1 immunostain, supporting the above diagnosis.

5/6/2024 GROSS DESCRIPTION: A. Received fresh, the specimen is labeled "liver biopsy mass X6" and consists of seven cores of tan-white tissue measuring from 1.0 x 0.1 x 0.1 to 1.3 x 0.1 x 0.1 cm. Four is/are submitted for ancillary studies. The remaining tissue is entirely submitted for routine histology. Summary of sections: A1 to A3. (SHS/CBS)

Shorehousejam profile image
Shorehousejam in reply to Shorehousejam

Tall_Allen see above

Seasid profile image
Seasid in reply to Tall_Allen

In this Astra Zeneca clinical trial parp inhibitors are successful against ATM mutation:

christie.nhs.uk/about-us/ne...

Shorehousejam profile image
Shorehousejam in reply to Seasid

Thank you

Seasid profile image
Seasid in reply to Shorehousejam

More info here ascopubs.org/doi/10.1200/JC...

Seasid profile image
Seasid in reply to Shorehousejam

Clinical trial information clinicaltrials.gov/study/NC...

Tall_Allen profile image
Tall_Allen in reply to Seasid

That is just an anecdote. It would be wrong to conclude that "parp inhibitors are successful against ATM mutation." While the experimental drug (AZD5305) might or might not be, none of the FDA-approved PARP inhibitors are effective against ATM mutations.

prostatecancer.news/2019/10...

Maxone73 profile image
Maxone73

if I remember correctly with ATM your response to PARPi is not as good as it is with BRCA but better than if you have no mutation. Actually some secondary analysis reported that also some non atm /BRCA mutants can benefit. ATR seem to work better: keep an eye on this trial aacrjournals.org/cancerdisc... from Bayer

But there are other being tested even if I think that many are tested for ATM mutation but in breast cancer and in combo with PARPi

Shorehousejam profile image
Shorehousejam

very frustrating

MoonRocket profile image
MoonRocket in reply to Shorehousejam

May I suggest you ask your MO why Keytruda would be effective for you. My assumption is your TMB. If this is above 10, then doctors can prescribe for PCA. If not, then I would ask what the treatment is supposed to gain for you. No one on this site has a crystal ball or personal insight into your specific conditions, only your MOs do.

Shorehousejam profile image
Shorehousejam in reply to MoonRocket

Where do I look for TMB above 10?

My mutations are in bio

MoonRocket profile image
MoonRocket in reply to Shorehousejam

TMB high (17.4 muts/Mb)

Shorehousejam profile image
Shorehousejam in reply to MoonRocket

Thank you Moon Rocket

Shorehousejam profile image
Shorehousejam

great site

ATM Frameshift - My Cancer Genome

Sisto profile image
Sisto

I agree with TA about considering Provenge. Another nice thing about it is the low/ almost zero SEs. I had it alone five years ago and it seemed to help significantly. Getting insurance to pay for it was another matter. Good luck whatever you decide!

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