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Advanced Prostate Cancer
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Precision medicine-how effective?

The fields of precision medicine and immunotherapy have come to realize that targeted therapies are capable of not only inhibiting tumor cell growth, but also promoting antitumor immunity by modulating the tumor microenvironment.

See this recent post from urotoday -

urotoday.com/recent-abstrac...

Has anyone had any experience with precision medicine?

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Also, I did find Darryl's post from 4 months ago with an interesting article about this topic, which was not very encouraging about precision medicine. Rutgers Cancer Institute has a dept focusing on this area. Reaching out to contact the dept head Dr Rodriguez to discuss.

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This is what the NCI Match trial is all about...16 cancers including prostate.....involves initial gene mapping, and then depending on the mapping, being put into the appropriate treatment group...then evaluating the outcomes....I am watching Checkmate 650, and many of the drug trials....MM310--a more tumor specific docetaxol, TAS3681 and TRC253--looking at blocking wild/mutated AR which might leave someone castrate sensitive for longer/ time unknown...HPN424 and their new treatment platform...lots to be hopeful about...vaccine trials.... like you, I am hopeful.... Thanks for posting...

Take care,

Fish

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Well, only recently, Whole Genome Sequencing (WGS) costs about $1000.00. That's just the start, then extensive analysis will commence, currently not enough data/evidence from WGS to really target "Precision Medicine", meaning customized treatment for a single person.

Although, your WGS will provide better insights , like which mutations you may have. So, this will improve precision somewhat, but the physician will say something like, "We think these xyz treatments has a good chance for you"...

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It does seem that the most common Dr response is "we just don't know". And that is why there are many clinical trials going on, with hopefully sufficient participants to result in statistically significant results. This is one of the reasons as to why I joined the SIMCAP trial.

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Good for you...trial participation is the key to knowledge advancement...Thank you for doing the trial. I participated in an apalutamide trial at Cleveland Clinic...Looking at the vaccine trials and will talk with my MO when I see him at the end of the month... I may see if I can participate in stereotactic radiation dependent on if/ when they find another bone mets and trial openings...

Take care,

Fish

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The problem is that we don't have the therapies tailored for each of the gene mutations implicated for prostate cancer - there are over 200 identified so far. As solutions for those rare men that have some of them, we have platins and PARP inhibitors for those who have mutations that affect DNA repair. Keytruda was recently approved for men with a very rare mutation (MSI-hi/dMMR). That's it so far. Hopefully, clinical trials will identify more. There are so many growth pathways, that when you inhibit one, the cancer cell thrives by eliciting another. It's very depressing.

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IMO I would rather use the term "challenging" than "depressing".

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Immunotherapy is no doubt the future of cancer treatment. There are many brilliant young minds up to this challenge not only working on it but welcome it.

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I hate to be negative once again, but, except for Provenge, immunotherapy so far has proved to be worthless for PCa. Maybe some of the combos will be worthwhile.

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Unfortunately you are correct however it is showing promise in other types of cancer and hopefully prostate cancer will follow suit. Actually I talked to a few specialists that said they haven't seen where Provenge is even anything special. This was an interesting find in current research for immunotherapy and aggressive prostate cancer. Might have to copy and paste the link.

medicalxpress.com/news/2018...

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It is a mistake to think that what works for one kind of cancer will work for others - they are all very different. There is some controversy about whether Provenge works at all - I think it does. However, other immunotherapies (eg. Prostvac, GVAX, Yervoy and Keytruda) have failed to show significant benefit. Your citation was about one of the 3 known personalized therapies - Keytruda for MSI-hi/dMMR. It is already approved in the US for that.

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I didn't mean it as prostate cancer is the same as other cancers and I understand cancer as a whole is very broad in treatment. It is definitely a direction cancer research is taking. If I may pick your brain, out of curiosity what is your opinion on the direction that treatment is going specifically for prostate cancer? Where do you think the future is in treatment beyond ADT?

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I'm partial to radiopharmaceuticals and other ways of targeting and killing prostate cancer cells. I'm also intrigued by microRNAs.

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Such as Xofigo, which contains Radium 223?

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Xofigo, AC-225-PSMA, Lu-225-PSMA, I-131-MIP-1095, Cu-TP3805, Cu-64-bombesin, Au-np and streptovirin attached to a PSMA ligand, docetaxel attached to a PSMA ligand, and probably a dozen more in clinical trials.

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I had provenge a year an a half ago,,I was told that it doesn't reduce psa,if you are alive in four years it worked, I did not say anything,

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Accepting Tall Allen’s statement that to date they have identified 200 PCA related mutations ( I dont know how many are germline ) and

If many those 200 mutated PCA cells further mutate it seems like a video game where once you shoot the bad guy he blows and yet reappears as someone else and the cycle continues indefinitely.

If true , targeting one mutation might slow tumor progression down until the other mutated cells became dominant. And even if you had a

200 medicines that killed the 200 mutated cells, further mutations could arise from one or more of the 200 dying cells.

And if that is also true, precision medicine is not applicable to PCA .

It would seem that the only way to permanently kill all PCA cells is to create a chemo to selectively kill the DNA repair mechanism of only the PCA cells .

If any of what I just said is true, I understand TA’s statement that contemplating enormity of the problem/ solution is “depressing”.

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So we need a chain reaction in which 1 dead cancer cell splits and kills 2 cancer cells which split and kill 4 cancer cells and etc. I think you are on to something here. Now we just need a bored Einstein to put it all together.

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I have a good friend who is a cancer research scientist focusing on immunotherapy. He told me that there are many positive developments using immunotherapy with different cancers but there has been little success so far applying it to prostate cancer. Scientists don't know why prostate cancer isn't responding as well as other types.

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Up to now we've been using what I call the atomic bomb approach to prostate cancer. Things like taxotere blow up everything in sight, but hopefully not as much of the good guys as the bad guys. Immunotherapy is more the sniper rifle approach. Just targets the bad guys. Unfortunately you need the right rifle, a good spotter/shooter team and a way to positively identify the bad guys. We're not there yet.

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At this point I can say that I had 72 radiations over 11 years and Lupron for 6 1/2 years and now I have no cancer.

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As I've posted before much to the dismay of some of you I am being treated for a stage IV lung melanoma with the Immunotherapy drug Keytruda. It is working. 15 sessions at $30K per pop. I have asked both my Pca Oncologist and my Melanoma Oncologist if it is benefiting my fight with Pca. Both replied NO. I am scheduled to see them both this month (January) and will ask them again if any benefit? I need some ice cream!!!

Good Luck, Good Health and Good Humor.

j-o-h-n Friday 01/04/2019 5:42 PM EST

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