Cancer cell dormancy: mechanisms and implications of cancer recurrence and metastasis

[pjoshea13]

Nalakrats recently reposted "CAN DORMANT PCA CELLS BE KEPT DORMANT".

I responded with a 2017 paper [1] which covers some of the ground that he intends to explore in the near future. He asked that I start a new thread by re-posting the paper:

"Cancer cell dormancy: mechanisms and implications of cancer recurrence and metastasis" [1].

I hesitated since many will find the paper hard-going. But I have added a few notes that might help.

...

Early in the Intro we read:

"The mitotic arrest precisely refers to cellular dormancy, suggesting that a G0–G1 arrest can exist in certain cancer cells."

Mitosis is cell division. The steps that culminate in the division of a cell into two cells is called the "cell cycle". It consists of the following phases:

- G0 - quiescence

- G1 - pre-DNA synthesis

- S - DNA replication

- G2 - pre-mitosis

- M - mitosis (division)

We hope that therapies result in cell death (primarily via apoptosis), but cell cycle arrest is fine too.

...

Reading further:

"The majority of DTCs {disseminated tumor cells} remain a state of quiescence. A subgroup of DTCs circulating in the blood is termed circulating tumor cells (CTCs), and some findings indicated that DTCs could hold a stem cell-like phenotype called cancer stem cells (CSCs ...)"

The concept of cancer stem cells was very new when I was diagnosed. At that time, none had been found in PCa & no-one knew how to look for them. Some doubted that they existed.

Some confusion still exists concerning CSC origins - are they stem cells that have become cancerous, or tumor cells that have developed "stemness".

There is a very old rat study where castration leads to involution of the prostate - it all but disappears. However, with testosterone treatment, the prostate grows back to normal size. Castration does not affect stem cells because they do not need androgen; they have no androgen receptor.

Castration, of course, is not a cure for PCa. The dominant view is that depriving the cancer of androgen drives some cells to retreat into a stem cell-like form.

But even today, researchers use the term "putative" CSCs.

...

{My wife is dragging me out to vote - so I am sending this as is.}

-Patrick

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

[curt504a]

Tnx Patrick!

Of course this is an important topic, mainly how to keep DTC's dormant, but there's cross wise issues in play as well. I went to several non-std of care cancer conferences in the Spring. It was mentioned that if you are post primary tumor cure, don't have any elective operations from that point on (nose jobs, boobs, etc etc). Other physical trama may mimic as well. The body being subjected to trama, the knife, etc, can activate the dormant DTC. Hmmm!!! IE the healing process has been seen to trigger either DTC activation OR the possible 2ndary/Tertiary cancers to kick in.

Which is why monitoring the various cancer markerts, PSA etc frequently post primary tumor is important. To monitor for the chemical signatures of DTC --> CTC --> cancer taking root somewhere.

i didn't catch the practitioners proprietary blood or CTC tests they also do frequently, but would be useful to create a testing protocol file here.

Not specific to PCA, other cancer's protocols, radiation, toxic chemo's cause a (some %) incidence of 2ndary and thertiary cancers in the following years. IE the chemo / radiation etc create NEW cancer down the line... I hope this is pretty much a settled issue that toxic choices may be useful near term but depending on luck and circumstances you'll have 2ndary cancers down the line unrelated to the species of the primary cancer.

I'm wondering if Nalkrat's quest for understanding keeping DTC dormant may be running cross wise to NEW cancers unrelated to the primary... Too much real patient data is needed AND then to eliminate the 2ndary/Tertiary cancers from DTC going active causing a reoccurance of the identical primary tumor species MET or same site. I feel its 2 difference scenarios; same species re-occuring from DTCs, and new species of cancer caused by toxic protocols.

A question I have: which is more probable (a meta study?? and I hate meta studies) dieing from activated DTC or 2ndary / tertiary new species of cancer. Its possible that DTC--> activation may be the lower probability event. Of course its a number representing probability what ever that number is, and not a certainty either way.

My interest is to understand knocking down CTCs, keeping DTCs dormant, and non-toxic protocols to avoid giving myself a new species of cancer down the line.

[cesanon]

Nice article. I'm going to have to spend some quality time with it.

It is disconcerting that the lead in indicates that there is not a lot of investigation that has been done in this subject area.

[curt504a in reply to cesanon]

The genealogy on why little research,,, my bet is:

- The FDA's 20+ yr old criteria for getting a cancer drug patent (which has NEVER (to my knowledge) been updated) is still: 10% reduction in primary tumor size. POOF you get a patent! It would be informative if Nalkrats et al would update me re cancer drug approval criteria today?

Some time ago, maybe long ago, we (they ??) figured out that BOTH quality of life, and length of life was loosely related to shrinking the tumor.

Drug companies no doubt beg/forbid the FDA from updating this outdated model for new cancer drugs... Their multi-decade process is entirely built on this model, 10% tumor size reduction, damn everything else.

No wonder CTC, 2ndary, tertiary cancers just don't mater, ,,,, perhaps literally (to the drug production process anyway). ;(

BTW re CTC knock down, I recommend adding this synergistic with std of care:

careoncology.com / book by a patient How to starve cancer/ Jane McLelland. Face book group: jane mclelland off label drugs for cancer. Unfortunately I have not called/worked with CARE re PCA. But cancer consumes energy, the CARE protocol knocks down all the nutrient pathways, so I suspect CARE would be useful. But needs a call for their patient results.

[curt504a in reply to curt504a]

PCA is helped per: careoncology.com/the-coc-pr...

The protocol costs are very low. Think $800 for the consultation, and the off patent drugs are very cheap: metformin, a statin, an old antibiotic, one more... Might be as low as $100/mo +/-.

[cesanon in reply to curt504a]

"10% tumor size" That must be what they require before you start charging people money for a drug. It has to be effective. They approve drugs for pain that don't do anything except reduce pain.

I would be surprised if it were that simple ("10% tumor size"). They have whole consulting companies that work on getting drugs approved.

I think the rule of thumb is that they have to develop 10 drugs in order to get one approved. But there are good reasons why those 9 never get approved.

Once the pharmas see an opportunity to use one of these pathways to make a drug, they will take it. It must be that the science isn't yet far enough advanced for them to do it.