Liquid Biopsy Method Enables Real-Time Monitoring of Metastatic Prostate Cancer…

[Maxone73]

….and can help in finding new targets for therapies!

insideprecisionmedicine.com...

[CousinGrandpa]

cool! Another use of mRNA.

[j-o-h-n]

On the rocks?

Good Luck, Good Health and Good Humor.

j-o-h-n

[garyjp9]

Thanks Maxone73. Will a liquid biopsy/circulating tumor cells come up positive even if your PSA is still undetectable but you are still carrying cancer cells that are not yet detectable?

[Maxone73 in reply to garyjp9]

Yes because they are based on mRNA from the cancer. I do not know if there is a threshold for detect ability but the system is not based on PSA

[skiingfiend in reply to Maxone73]

I have had 2 ctDNA tests run under a research protocol. Here are the results to give you a feel for what can be reported. ctDNA tests are used to identify point-in-time somatic mutations which may be related to specific treatment options. ctDNA enables personalized medicine which more specifically targets your cancer and its mutations than systemic therapy.

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To date, we have sequenced two of your samples: 8/NOV/2022 (just prior to you starting ADT injections) and 13/FEB/2024 (when you developed liver metastases).

1. Germline mutations

We saw the germline CHEK2 mutation that you inherited. This was expectedly observed in both samples (your germline DNA doesn't change over time).

2. Tumour fraction

Think of this as the proportion of the free-floating DNA in your blood that is tumour-derived. In the first sample, it was ~10%. In the second sample, it was ~40%. Note: these are merely estimates, there is a degree of uncertainty around these results. I think the main take home message is the tumour fraction did go up significantly between your first and second sample. Of course, this fits with what we saw on your scans. Another thing to be aware of is that an increase from 10% to 40% does not mean that the amount of cancer has increased four-fold. It just means that the tumour is dividing at a faster rate at the time of the second sample compared to when we took the first sample. Again, this seems consistent with the diagnosis of small cell prostate cancer.

3. Somatic mutations

- In the first sample, we saw mutations in CTNNB1 (Missense p.S33A), KMT2C (Stopgain p.Q957X), KDM6A (Frameshift p.F62Wfs*16), and KDM6A (Stopgain p.S1348X).

- In the second sample: despite an increase in the overall tumour fraciton, we were only able to 'rediscover' the KMT2C (Stopgain p.Q957X) mutation. It suggests that the cancer cells carrying the CTNNB1 and 2 x KDM6A mutations were wiped out from your original treatment (or are still present but a very, very low level), but the cancer cell population harbouring the KMT2C mutation has persisted and risen to be the dominant clone. No other mutations were seen in this second sample.

- None of these mutations described in this Somatic mutation section are clinically actionable. That is, none of them are directly tied to any specific targeted therapy.

4. Other alterations

- We saw evidence that your tumour had lost all copies of PTEN, which is a tumour suppressor gene. We do see this in small cell prostate cancer, and can be accompanied by genomic alterations in TP53 and RB1. We did not see any biologically relevant alterations in TP53 and RB1 from your tumour.

- Tumours with PTEN deletion cause activation of the PI3K pathway, which is a major growth pathway. Hyperactivation of the PI3K pathway is potentially targetable with inhibitors against this pathway. Some of them in testing include capivasertib (AKT inhibitor) and ipatasertib (AKT inhibitor clinical development was halted last year though unfortunately). These drugs have been tested in prostate adenocarcinoma (attached most relevant paper) - there really isn't any data to support its use in small cell prostate cancer.

Note: these results are research findings only, and technically can't be used to directly inform your care unless there is confirmatory clinical grade testing.

All in all, I don't think the genomic testing you performed adds any additional information to inform your care. It was critical to perform, but I would stay on the current treatment, and focus on small cell therapies.

[garyjp9 in reply to Maxone73]

Thank you

[garyjp9 in reply to Maxone73]

thank you

[Seasid]

My first oncologist in 2018 when I asked him about circulating tumor cels said very angry that it is rubbish.

Watch this video:

urotoday.com/video-lectures...

[Cancer2x in reply to Seasid]

Know what they call the guy who finished last in his class in Medical School?

“Doctor”

[Maxone73 in reply to Seasid]

It was 2018….some friend at Trento university developed a liquid biopsy that can predict neuro endocrine cancer…in 2024

[Seasid in reply to Seasid]

That is really great but people are not dying from the CTC s. You could still live a long life. In the video they say that even after the first on the scans visible Mets if you are not de Novo metastatic you can expect to live at least 8 years and possibly much longer. Therefore CTC etc. Should not be a biggest concern. Of course I am trying to get rid of them by different ways.

Therefore even after the first visible Mets if you are not de novo metastatic you are expected to live 8 years.