Cancer cells may evade chemo by going dormant

[noahware]

This study involved acute myeloid leukemia, not PC, but the principles involved may translate to some extent: medicalxpress.com/news/2021...

Not sure this article has any practical application for any of us (yet) but I thought it was interesting to consider that as much as we might want to "put our cancer to sleep" temporarily, to delay progression and relieve symptoms, there are also times when we want our cancer cells to NOT be in a state of hiding/hibernation... namely, when we are trying to kill them with chemo.

Could this mean chemo or ADT might be less effective when done concurrently, rather than sequentially, since either one of those therapies might be inducing a protective state of senescence that limits the overall kill rate by the other therapy? Or am I way off on that?

An excerpt:

"For years, cancer researchers have studied how tumors are able to rebound after they appear to be completely wiped out by chemotherapy. One theory has been that because not all cells within a tumor are the same at the genetic level—a condition called tumor heterogeneity—a small subset of cells are able to resist treatment and begin growing again. Another theory involves the idea of tumor stem cells—that some of the cells within a tumor have special properties that allow them to re-form a tumor after chemotherapy has been given.

The idea that senescence is involved does not replace these other theories. In fact, it could provide new insight into explaining these other processes. Researchers found that when AML cells were exposed to chemotherapy, a subset of the cells went into a state of hibernation, or senescence, while at the same time assuming a condition that looked very much like inflammation. They looked similar to cells that have undergone an injury and need to promote wound healing—shutting down the majority of their functions while recruiting immune cells to nurse them back to health.

These characteristics are also commonly seen in developing embryos that temporarily shut down their growth due to lack of nutrition, a state called embryonic diapause. It's not a special process, but normal biological activity that's playing out in the context of tumors.

These findings have implications for developing new drug combinations that could block senescence. Further research revealed that this inflammatory senescent state was induced by a protein called ATR, suggesting that blocking ATR could be a way to prevent cancer cells from adopting this condition. Two other groups reported that the role of senescence is important not just for AML, but for recurrent cases of breast cancer, prostate cancer and gastrointestinal cancers as well."

[LearnAll]

Thought provoking post ! This brings us to the age old debate of sequential vs all at once treatment. You will find advocates of both these approaches,There is a third way also. That is ...Hit it hard but do not keep hitting continuously. (intermittent therapy) Every man's cancer is unique and treatment sequence and timing has to be tailor made for each. One size (aka SOC) does not fit all.

[immunity1]

No I dont think that you are way off at all. The sequence of treatment is very much up in the air except for very specific comparisons in cohort, prospective trials which do not generally fit many of our individual circumstances.Certain sequential treatments appear to be more 'easy on the body' with less side effects than combination treatments.

Theoretically at least adaptive treatment seem logical to me if you have a reliable indicator (PSA),, as per Zytiga.

DOI: 10.1038/s41467-017-01968-5

[TFBUNDY]

I tried going dormant to evade work but my wife woke me up...

[Seebs9 in reply to TFBUNDY]

I think I married her sister.

[reb77 in reply to TFBUNDY]

My wife thinks I'm dormant, but at the cellular level I'm actually very busy!

[TFBUNDY in reply to reb77]

Good excuse. Stick with it...

[RonnyBaby]

It is an interesting theory / concept .....

Next is to try to prove it in trials .....

[CSHobie]

I think this has a lot of merit.

Thinking about spraying weed killer on your lawn, it works best when the weeds are growing strong and green, not during a drought period for example.

I do think its likely that Cancer behaves similarly.

[GeorgeGlass]

This is what I have been saying about treatments. Some guys treat the cancer like it is a dumb disease but how can you call it dumb when it has the ability to mutate during each new type of treatment. My cancer started to grow 10 times faster immediately following initial treatment with radiation. I would have been better off doing nothing then to do what I did. During immunotherapy treatments on cancer, the cancer is sometimes completely eradicated from the body, only to come back 100 times stronger and kill the patient within two weeks or less. that is not a dumb disease that always behaves the same during new treatments. Thus, just because a study shows average outcomes, it does not mean that those result necessarily apply to everyone, because each person's cancer is a little different. What do you think? Am I off base?