Stable disease - how much do we understand about the mechanisms underlying it? - 1250659

ailsajr
Posts:2

Hi, I've reached a stage where if I visit the oncologist after a scan and I am told "it shows stable disease", I come away feeling relieved and thankful. :-D

I have a number of mets (of rectal origin) which have remained pretty well unchanged since diagnosis, in spite of two courses of chemotherapy, for which I am very grateful (despite initial disappointment back in the early days when I maybe hoped for a better response... ).

I'm curious about this state of affairs and why it happens. How much do we understand about the mechanisms behind "stable disease"? Why do some tumour cells almost appear to "go to sleep" - neither proliferating significantly nor dying off? Does it relate to turning off of apoptosis (programmed cell death) in tumour cells, cell cycle arrest, or what?

Thanks,
AJ.

Forums

certain spring
Posts: 762

ailsajr, I'd like to second your excellent question. As lay people, we seem to rely too much on the concept of tumour cells being 'dead' or 'alive' , when they may be - as you say - 'asleep' or 'resting'.
Best wishes for your continued stability.

Dr West
Posts: 4735

I would say that there are many possibilities. Besides achieving a state of "stasis" -- neither growing and dividing nor shrining and dying -- you can see stable findings if the process of cell division is in equilibrium with the process of cell death. In truth, this is really not known, and it likely varies with different treatments and from one cancer to another. Essentially, this level of molecular detail is not known to practicing clinicians or probably anyone. It may be studied in a lab-based setting, but those people are likely studying the activity of these agents in cell lines or animal models rather than in real people with actual, clinically relevant cancers.

I'm sorry I can't say more. That's just not a question that we can answer from the perspective of the cancer clinic in late 2012.

-Dr. West

drquesnelle
Posts: 4

Hi AJ,

When we study drugs, we categorize the effect of the drug as being cytotoxic or cytostatic meaning whether the drug reduces cell number or just maintains cell number and prevents increases in cell number, respectively. As you have pointed out, increases in cell number can be due to either decreased apoptosis or increased cell division (proliferation), or a combination of both. While cytostatic drugs can maintain cell number through altering either of these processes, they can also drive cells into senescence, which is scientific term for arrested cell growth. Senesence is a normal process in cells as they age. Typically, cells go through the cell cycle a certain number of times and then senesce. At this point, the cells are no longer proliferating but they aren't dead yet, either. What happens inside a cytostatic tumor is much like this, I'd imagine. While many of the cells in the tumor may eventually die, unfortunately some may re-enter the cell cycle due to acquired mutations or extracellular factors in the tumor microenvironment. This is why it's impossible to answer your question definitively. As Dr. West points out, the nature of the "stasis" can vary depending on the drug used for treatment but I would add that it can also vary over time within the same tumor (as mutations are aquired) and from cell-to-cell within the same tumor (depending on extracellular factors) which is why it isn't really studied in people or in animals, for that matter. It's just too dynamic for our technology right now. Regardless, not progressing is a good thing no matter what the reason behind it!

All the best,

Kelly

Paulina
Posts: 20

Thank you, ailsajr, for your interesting question. Thank you doctors for the good answers.
Stable news from the doctor make me relieved and happy too. I have been stable since June 2009 until today with 43 Alimta treatments. Since March 2012 I have had a break in my treatments and I'm still stable.
I wonder if my many Alimta treatments have driven my cancer cells into senescence, but I know that it is a matter of time that mutations may appear.
Wishing stable or even better news for every one,
Paulina