I came across this yesterday:
"Epigenetics-based diagnostic and therapeutic strategies: shifting the paradigm in prostate cancer" 3/28/23 Epigenomics [1]
From the intro:
"Clinically, PCa screening methods display low sensitivity and specificity, leading to suboptimal patient care."
We are still very much in the PSA era, and they have been saying similar things for about 35 years.
"Recent research suggests that PCa progression is regulated by a coordinated spectrum of epigenetic alterations that notably involves noncoding RNAs."
"Epigenetic proteins and noncoding RNAs can be detected noninvasively in body fluids, allowing improved PCa screening and prognosis. In addition, epigenetic alterations can be targeted pharmacologically, providing unprecedented therapeutic opportunities."
I started seeing my integrative medicine guy in 2006, because he supported my use of androstenedione to increase testosterone. One of the tools he liked to use for new patients was a hair analysis. When I next showed him blood test results from my annual medical, he was appalled that my doctor had not acted on my elevated homocysteine. He checked the list of minerals in the hair analysis & noted that I had zero cobalt in my hair. He concluded that my stomach was not making intrinsic factor & that consequently, my gut was not taking up Vitamin B12, which meant that I was not able to adequately recycle homocysteine back to methionine.
He suggested that I inject B12 into belly fat periodically. For $24, I received a 6 month supply of B12 & syringes, plus training. What could go wrong?
The androstendione was keeping testosterone at about 1,000 ng/dL & chrysin was keeping estradiol at about 20 pg/mL. I was testing PSA monthly & I had six identical readings of 0.8.
In the months following B12 injections the monthly PSA increased to 0.9, 1.0 & 1.2. Might B12 be the reason?
Sure enough, there were Swedish papers on the topic. A good folate & B12 status was associated with more aggressive PCa progression, whereas a poor homocysteine status was seen to be protective.
The SAM (SAMe) cycle is roughly:
methionine--->SAM--->homocysteine---> +folate +B12---> methionine
SAM is the universal methyl donor in the body & folate (or folic acid) is the common methyl donor in the diet.
PCa cells are avid for methyl. The DNA promoter regions for tumor suppressor genes are never methylated in normal prostate cells, but become hypermethylated in PCa - when the SAM cycle is working. (If it ain't working, don't fix it!)
Hypermethylation is an epigenetic change. DNA is not altered, it is simply silenced. Epigenetic changes can be reversed. I discovered that genistein was a demethylation agent. I took high doses.
Slowly, my PSA doubling time increased from a few months to slightly over 2 years. It took longer to return to a poor B12 status. Alcohol helped in that regard.
I kept reading about many of the changes that occur in PCa cells being epigenetic - not mutations. The future looked bright. Epigenetic drugs were just around the corner. Epigenetic changes were going to be reversed. PCa was going to become easier to manage. But it hasn't happened.
There are almost ten thousand PubMed hits for .
There are only three hundred for .
M. Clermont seems not to have written on the subject before. How many will read his review? How many even subscribe to Epigenomics?
-Patrick
[1] pubmed.ncbi.nlm.nih.gov/369...
Review Epigenomics. 2023 Mar 28. doi: 10.2217/epi-2023-0045. Online ahead of print.
Epigenetics-based diagnostic and therapeutic strategies: shifting the paradigm in prostate cancer
Pier-Luc Clermont 1
Affiliation1Université Laval, Québec, QC, Canada.
PMID: 36974615 DOI: 10.2217/epi-2023-0045
Abstract
Despite recent advances, prostate cancer (PCa) remains a leading cause of cancer morbidity and mortality. Clinically, PCa screening methods display low sensitivity and specificity, leading to suboptimal patient care. Recent research suggests that PCa progression is regulated by a coordinated spectrum of epigenetic alterations that notably involves noncoding RNAs. These molecular aberrations drive PCa progression by inducing gene expression programs that promote metastatic dissemination. Epigenetic proteins and noncoding RNAs can be detected noninvasively in body fluids, allowing improved PCa screening and prognosis. In addition, epigenetic alterations can be targeted pharmacologically, providing unprecedented therapeutic opportunities. This work reviews the current literature linking epigenetic dysregulation and PCa progression and proposes a framework for integrating epigenetic strategies into the clinical management of PCa.
