Your thoughts on epigenetics?

[Mascouche]

I've read that genes are a gun and epigenetics are the trigger. I am curious as to whether you think this is hogwash or not. Can people truly turn off bad genes (like BRAC2 mutations) and turn on good genes that might help fight off cancer through epigenetics?

[pjoshea13]

Epigenetic changes are not hogwash. Cancer finds ways to silence tumor suppressor genes other than by mutation. A common epigenetic change is methylation of the protective gene promoter regions (in the CpG islands), which are never methylated (silenced) in normal cells.

In the case of methylation - & PCa cells like to be hypermethylated, which is why I have written a lot about dietary methyl donors, such as folic acid - the hope is that a safe & effective demethylation agent will be developed; see [1]. Genistein is a natural demethylation agent, at high doses [2] [3] - at least in the lab:

Genistein Increases Estrogen Receptor Beta Expression in Prostate Cancer via Reducing its Promoter Methylation

Genistein reverses hypermethylation and induces active histone modifications in tumor suppressor gene B-cell Translocation Gene 3 (BTG3) in prostate cancer

But you mention "BRAC2 mutations", which are not due to epigenetic alterations, & therefore not reversible.

The good news is that many of the changes that occur in PCa are epigenetic (occurring above the gene level without changing them.) The bad news is converting the large amount of information we have into a therapy is taking forever.

-Patrick

[1] en.wikipedia.org/wiki/Demet...

[2] ncbi.nlm.nih.gov/pmc/articl...

[3] ncbi.nlm.nih.gov/pmc/articl...

[BruceSF in reply to pjoshea13]

I ran across a paper on brca methylation in ovarian cancer - it does happen sometimes, and they are going to try olaparib. res.mdpi.com/d_attachment/i...

[HopingForTheBest1 in reply to BruceSF]

I am BRCA2+. Was on Olaparib for almost 2 years, very effective at keeping my PSA undetectable, until it ran it's course. Nothing lasts forever, especially if you are BRCA2+.

I keep working on finding a viable Plan B treatment option, but it has been very elusive.

[Bigblock]

The principal is right, take a butterfly, it changes form a caterpillar to a butterfly through a series of turning genes off and turning others on, but as Patrick says it’s taking so long to get a therapy together

[Mascouche]

Do you think food and environmental changes can impact epigenetics or just pharmaceutical drugs?

[Hidden]

Brac2, that means HRD, perhaps POLQ is upregulated. DFarber will start a trial using Novobiocin, blocks mmej. If you have Pten Loss the nhej is blocked additionally. Have yourMD contact DF.