Prostate cancer metastasis linked to revival of dormant molecular program activated first in fetal development

[fmenninger]

news.harvard.edu/gazette/st...

[timotur]

Fascinating... thanks for posting!

"It shows that particular programs that were operative during prostate fetal development become reactivated during metastatic disease,” said Matthew Freedman, a Dana-Farber medical oncologist and co-corresponding author of the report. “The reactivation of these programs is presumably important for the spread of the disease, and if we could understand it better, and potentially block or inhibit the process, it may help us to suppress metastatic prostate disease.”

[pjoshea13]

Reading the article, John Ruskin's term 'the pathetic fallacy' comes to mind. i.e. assigning human attributes to nature. He was thinking more of angry thunder claps rather than crafty efficient cancer strategies - all three words appear in a single sentence.

"The Hayflick Limit is a concept that helps to explain the mechanisms behind cellular aging. The concept states that a normal human cell can only replicate and divide forty to sixty times before it cannot divide anymore, and will break down by programmed cell death or apoptosis." [1]

At the ends of each chromosome, there is a structure (telomere) that is comprised of DNA repeats. With each cell division, the telomere is shortened by one or more of the repeats. Eventually, the telomere becomes too short for cell division to occur.

The obvious explanation for this clunky mechanism is that cells that have a rate of division (higher than their mortality rate - & this includes cancer) are a liability to the host. But this is exactly what must occur in the womb, so fetal cells produce telomerase, an enzyme that facilitates the maintenance of telomere length.

A weakness of the telomere safety net is that it selects for cells that look more like fetal cells. Restoration of telomerase is an important step. The first mention on PubMed is in 1996 [2]:

"Telomerase activity: a prevalent marker of malignant human prostate tissue"

We have known for some time that many of the differences between PCa & normal cells are due to epigenetic changes - not genetic mutations.

"“As the cancer cell searches for ways to grow and metastasize, it appears to access and hijack the program that is most easily ‘visible’ — the bookmarked developmental site,” explained Mark Pomerantz, co-first author of the report."

"We were amazed ..."

Why?

Occam's Razor [3] demands that this explanation be considered first.

-Patrick

[1] embryo.asu.edu/pages/hayfli...

[2] cancerres.aacrjournals.org/...

[3] britannica.com/topic/Occams...

[BruceSF in reply to pjoshea13]

Thanks for the great detail, PJ. Also, I found a short video of Dr. Pomerantz discussing the findings at homehealthchoices.com/prost...

Generally, it looks like epigenetics will be the 'next big thing' in personalized medicine - there seems to be a lot more information in the methylation and chromatin patterns than there is in the mutations. My own hope is that it will soon show who should get chemo for advanced pc and who will do better on abiraterone, or maybe appalutamide.

[pjoshea13 in reply to BruceSF]

Hi Bruce,

The link failed for me, but I found this with Matthew Freedman, MD (Dana-Farber Cancer Institute)

homehealthchoices.com/prost...

He does a far better job than I did [LOL]

-Patrick

[BruceSF in reply to pjoshea13]

Thanks Patrick. Actually, my link was the same one, i.e., Dr. Freedman. I think the redirects on healthunlocked aren't working today for some reason.