RB1

[Blair77]

Hi,

So at my husband;s last biopsy (lesions on the bone) for a clinical study it was found that he now has this mutation also in addition to PTEN & TP53 . While this seems to be related to poorer OS ( like he didn't already have that going on) has anyone read anything about targeting this gene?

Thanks all,

Blair

[Hidden]

I found an article from 2015 that covers several mutations and treatments available. There has probably been progress made since then, but it has useful information.

sciencedirect.com/science/a...

[tango65]

These could be potential trials for PTEN.

clinicaltrials.gov/ct2/show...

clinicaltrials.gov/ct2/resu...

clinicaltrials.gov/ct2/resu...

clinicaltrials.gov/ct2/resu...

clinicaltrials.gov/ct2/resu...

[pjoshea13]

RB1 is a tumor suppressor gene. Seems that it is not too uncommon for it to be silenced along with PTEN & P53 in treatment-resistant cells.

The silencing is usually due to methylation. This is an epigenetic change & is reversible in theory. There have been threads on methylation. PCa cells tend to want to be hypermethylated. Depriving them of unlimited methyl is difficult in the U.S. & countries that followed the FDA lead of fortifying grains with folic acid. Folate is the primary methyl donor.

Men with low vitamin B12 are at an "advantage", since B12 is an essential cofactor in the recycling of homocysteine that leads to SAM (SAMe), which carries methyl to cells that want it.

High doses of genistein may demethylate cells. For a while, it looked like Disulfiram (anti-alcohol drug) might be useful [1] [2], but results were disappointing.

-Patrick

[1] ncbi.nlm.nih.gov/pubmed/208...

[2] ncbi.nlm.nih.gov/pubmed/239...

[cesanon in reply to pjoshea13]

Hmmm

So it would follow that anyone with these mutations should avoid US wheat products? Probably not bad as a general rule for anyone.

What are natural sources of genistein.

[pjoshea13 in reply to cesanon]

Rice is fortified too.

lifeextension.com/Vitamins-...

-Patrick

[cesanon in reply to pjoshea13]

Rice is fortified with vitamin B12?

[pjoshea13 in reply to cesanon]

Not B12 - folic acid.

[cesanon in reply to pjoshea13]

"The three major isoflavones found in soybeans are genistein, daidzein, and glycitein. Other isoflavones found in soy include diadzin, glycitein, glycitin.". Lef.org

Patrick, you mention genistein as being helpful to reduce methylization.

Do any of the other isoflavones have similar effects?

If so wouldn't a diet consistently supplemented with edamame do the job? Though I have heard too much soy can cause unintended hormone related imbalances.

What do you think about just pure genistein supplementation?

[pjoshea13 in reply to cesanon]

Daidzein is rated highly, but most in the West are not equol producers, so daidzein is not an option.

Dietary soy does not deliver enough genistein & is thought to promote PCa & BCa growth. Genistein has a biphasic effect in the lab. Pharmaceutical levels are required to inhibit PCa growth.

Which is why I only use the LEF product. If you find a product with more, please let the group know.

-Patrick

[cesanon in reply to pjoshea13]

How about this Patrick?

Amazon.com: Swanson Genistein from Sophora Japonica 125 mg 60 Veg Caps 3 Pack:

amazon.com/Swanson-Soy-Free...

[pjoshea13 in reply to cesanon]

I'd take 4 daily.

[cesanon in reply to pjoshea13]

But you still prefer the life extension product?

Why is that?

[CalBear74 in reply to cesanon]

Drink your soymilk at every meal for genistein.

[Ahk1 in reply to cesanon]

I eat oat meal for breakfast every day. Is that bad? I never did gene mappings. Thanks

[Jbooml in reply to pjoshea13]

My question with (de)methylation is what the heck are the global effects...the reactivation of wanted helpful genes also implies the activation of those not so much...all in the milieu of rapidly dividing mutating PC cells....?

[pjoshea13 in reply to Jbooml]

There is substantial collateral damage with conventional PCa therapy. I have used the LEF product for many years without side effects. I can't say how effective it is though.

-Patrick

[Jbooml in reply to pjoshea13]

The question begged is if its realistic to uncover the grandfather gene (ant)/agonist to halt these f'in variants.

[tango65]

Contact The Memorial Sloan Kettering Cancer Center. They have this potential trial for PTEN:

mskcc.org/cancer-care/clini...

PTEN mutations affect the PI3K and AKT pathways. This trial is for people with mutations in the AKT pathway.

[tango65]

This could be for PTEN and prostate cancer:

mskcc.org/cancer-care/clini...

[msnik]

Hello Blair,

I just read this within the past week:

".....therapy induced progression of prostate cancer to CRPC leads to two distinct tumors subtypes based on clinicopathologic and genomic characterization."

......

........"The second subtype, aggressive variant PCa (AVPC), is phenotypically similar to small cell prostate cancer with loss of AR expression, gain of neuroendocrine or pro-neural marker expression, sensitivity to chemotherapy and combined alterations of PTEN, TP53 and RB1 tumor suppressor proteins. "

urotoday.com/recent-abstrac...

I wish you and your husband all the best. I don't think my answer is responsive to your question, but it might help explain what "RB1" is to someone (like me) who had never heard of it before.....