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Darwin's cancer fix

RonJT
Posts: 36
Joined: Feb 2011

https://www.scientificamerican.com/article/darwins-ideas-on-evolution-drive-a-radical-new-approach-to-cancer-drug-use/

Principles of evolution and natural selection drive a radical new approach to drugs and prevention strategies

 
Max Former Hodgkins Stage 3's picture
Max Former Hodg...
Posts: 3328
Joined: May 2012

Ron,

I did not read the whole article, since I have no interest in paying them (subscribing).  I know that S.A. is considered first rate, but the claim that "Three-Quarters of Men with the Disease Succum to It" is ridiculous and something that all readers here know to be false.

As a disclaimer I repeat that I have not read the article, but suspect that it is more a "radical new" insurance and political proposal, than a rational-medical one.

https://seer.cancer.gov/statfacts/html/prost.html

max

VascodaGama's picture
VascodaGama
Posts: 3045
Joined: Nov 2010

I do not know how much Max’s opinion above is valid but I would think that the article at the Scientific American refers to those patients with metastatic cancer who have failed radical treatments and to whom chemo or ADT did not do well due to genetic mutations. The 3/4th numbers in death count could be from the small number of systemic patients in PCa cases. One needs to read the whole article buying the magazine or inquire the authors.

This sort of involvement of the Darwin’s principle on "natural selection" in both; the formation of cancer and its resistance to treatments, is well understood from the superb works of the Nobel laureates in medicine (2018), Dr. James P. Allison and Dr. Tasuku Honjo. They found those switches in cells that allow or prohibit the killing of a cell.

Regarding the authors of the article; James DeGregori is a doctor and professor in Biochemistry. He is a researcher and has written about biological processes at the cellular and molecular levels. Robert Gatenby is a nuclear physician specialist in imagenology. He is also a researcher and wrote several articles based on Cancer Biology and Evolution, which themes applies chemistry, physiology, and biology to investigate the chemistry of living systems and molecular genetics.

In any case, the title of this thread made me curious as I have also researched deeply and written before in this forum (in 2011) on the Darwin’s theory in PCa matters. Surely things have developed much along these years in regards to the genetics and their influence in cancer affairs. We know now more and what used to be pilot projects are now fully settled treatments with successful outcomes. You can read some of my discussions in this link;
https://csn.cancer.org/comment/1013947#comment-1013947

Thanks RonJT for posting this subject.

Best to all,

VGama

Georges Calvez
Posts: 307
Joined: Sep 2018

Hi there,

The article does refer to the small number of men who have cancer outside the prostate and it's immediate area at diagnosis, obviously the prognosis for many of these unfortunate individuals is bleak in many cases as they have extensive metastases in the bones or internal organs, it is often the case that they have a high Gleason Score as well.
I don't know where they got the 31,000 from either. This article claims around 175,000 of which 10% eg 17,500 will be very high risk metastatic cases and have a good chance of dying from the disease. Of the remaining 90% a good proportion will be cured completely and many others will manage to live with the bandit for many years before expiring from other causes.
https://www.cancer.net/cancer-types/prostate-cancer/statistics

Best wishes,

Georges

PS: I have bought two tickets for myself and my wife to see the Irish dancing
http://www.213productions.fr/irish-celtic-quimper/

lighterwood67's picture
lighterwood67
Posts: 219
Joined: Feb 2018

Robert Gatenby, he is a radiologist by training and heads the radiology department at the H. Lee Moffitt Cancer Center in Tampa, Florida.  He is studying theoretical and experimental models of evolutionary dynamics in cancer and cancer drug resistance and a tumor's physical microenvironment.Gatenby felt there must be a better way to treat cancer—to outsmart it rather than carpet-bomb.    Gatenby was concerned with the treatment of cancer in some cases killing the patient.  A friend of his came to the clinic on a Friday, took his treatment and was dead by Monday.  My cut is more power to the researchers if they can find a way to treat the prostate cancer effectively without gutting or nuking the cancer then more power to them.  To me, it is kind of like this, you go out there and try to totally take out that fire ant mound.  Looks like you killed them all.  In a week or so they are building another mound. Anyway, hope this is not too trivial for some of you folks.  Please look Robert Gatenby up.  You may find it interesting reading.

 

Georges Calvez
Posts: 307
Joined: Sep 2018

Hi there,

The techniques have certainly got better but they still remain close to what they were at the beginning of treatment for prostate cancer.
A real advance short of a cure would be stopping androgen independence developing, this would turn men with some metastatic cancer into essentially patients with a chronic illness that would likely die from other causes from the present situation where we can hold it in some cases but others progress, sometimes quite rapidly.
The problem is that androgen independence is like prostate cancer itself a many headed hydra, cancer cells have a variety of mechanisms for dealing with a low androgen environment and still growing.
I think genetic testing offers some promise. For a start may enable us to differentiate between slow growing non malignant cancers and the real trouble makers. Gleason Scoring is only a crude tool for doing this. Urologists could then say with confidence that a cancer could be safely watched as a course of treatment instead of moving to active treatment like surgery, etc. Hopefully it may also allow more targeted therapies as well.

Best wishes,

Georges

VascodaGama's picture
VascodaGama
Posts: 3045
Joined: Nov 2010

Lighterwood;

Your post on Robert Gatenby is very interesting and not trivial at all. It seems that he has at his own disposal the whole facilities at Moffitt Cancer Center so that he manages to use the laboratories in his researches. The staff also may be working under his directions. Interestingly he uses mathematics in oncology models probably creating them for uses by other researchers. One of my good friends here is an applied mathematics professor that has been involved in creating mathematic models for medical researchers at Tsukuba University in Japan. Surely I will take the opportunity in obtaining from him some news on recent studies regarding PCa. I enjoyed watching the video on Imaging Tumor Heterogeneity.

https://www.pathlms.com/wmis/events/625/video_presentations/34022

 

Georges;

I also think that more researches should be done on the dependency that prostatic cells have in androgens. Regulating its dependency could lead in balancing low or high activity of prostatic cells. Indolence could be induced in manners lesser invasive than the typical treatment used today.
So far, much has been done in the sense of avoiding prostatic cells from absorbing the stuff (for their survival) but nothing proper has been done to change its dependency on androgens. In genetic studies researchers have identified some genes involved in mutations (at the androgen receptors of cells) but nobody speaks on findings that turn cells indolent when some sort of genes are not present.

Treatments also are based in diminishing or avoiding the amount of testosterone in circulation, or avoiding its absorption by cells. This is still the present standards of ADT that come from 1941 when Charles Huggins discovered PCa dependency on testosterone for survival.

Many factors are involved and the mechanism of the endocrine system is complicated. Please read these links;

https://www.mdpi.com/2305-6320/6/3/82/htm

https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0023144

Best

VGama

Clevelandguy
Posts: 471
Joined: Jun 2015

Hi All,

Found another article by NCI about ADT that talks about how cancer mutates and adapts.  Nature will try it's best to adapt and survive.

https://www.cancer.gov/types/prostate/prostate-hormone-therapy-fact-sheet#how-do-hormones-stimulate-the-growth-of-prostate-cancer

Dave 3+4

Georges Calvez
Posts: 307
Joined: Sep 2018

Hi there,

Interestingly the prostate goes through several periods of slow and rapid growth during a man's life so that if you live long enough some prostate problems eg BPH or difficult urinary flow are almost inevitable.
http://www.asiaandro.com/archive/1008-682X/4/269.htm

Best wishes,

Georges

VascodaGama's picture
VascodaGama
Posts: 3045
Joined: Nov 2010

Dave,

The mechanisms behind such natural capability of adaptation, existent in the biostructure of all our building blocks (the cells), is the key that one day may guide us in finding the silver bullet to eliminate cancer. Those identified switches providing survival to cells is just part of the mechanism they own that oblige them into adaptation.
I compare this behavior to a jigsaw puzzle where one piece manages to fit into a hole but does not fill the entire opening. In cells behavior, the empty space is later filled with materials of adjacent pieces. This represents the capability cells have in adapting to the situation in a manner that they will repair what is in fault or alter their own means of survival. Death is never a prime goal in cells behavior but evolution for continuing living. They strive to reach the best and got the means to avoid destruction no matter what we throw at them, as we presence in RT or Chemo failures.

In hormonal treatments, the work of Lupron and other agonists do not directly involve the cancer. Antiandrogens like Casodex do act on the cancer but do not address their capability in survival. They are faked androgens made of a similar biostructure of the real ones which leads cells to absorb them (stacked to the androgen receptors). This works well during a period until the moment that cells feel their survival threatened and start their natural means to adapt or repair. We call that timing refractory of the treatment.
In adaptation mood, cells initially manage survival by feeding in low volume of androgens increasing it latter by feeding on the faked androgens (we take) or start producing androgens by themselves. Once such mechanism unfolds there is no way to stop it and the cancer spreads rapidly invading other organs till the death of the individual.

The present hormonal therapies aim indolence instead of aiming death or repair of the bad cells. It is a palliative approach that does not address the problem but try extending life of the individual. Better than ADT are the resent treatments involving Mabs. These Monoclonal antibodies are modified molecules that can substitute or mimic the immune system's attack on cancer cells. Cells respond to any initiative by the immune system so that one manages to turn off some of the survival-switches of cells, allowing a better job by the chemicals or radiation we throw at them. Unfortunately those switches also promote cells to adapt and some of these manage to survive.

Best to all,

VGama

 

Georges Calvez
Posts: 307
Joined: Sep 2018

Hi there,

There is a link between Gleason Score and the time to androgen independence just like there is a link between Gleason Score and metastases.
Low Gleason Scores take longer to reach androgen independence just like they metastase less readily.
This is because they are more like normal prostate cells with high androgen dependence, Gleason 10 cells have really thrown off almost all of the properties of prostate cells and are getting on with the serious business of being cancer cells.
It is also worth noting that ADT with radiation is more effective with grade 8 and below in comparison with grade 9 and 10. One could suppose that lower grades suffer more from the androgen deprivations so are more susceptable to the effects of the radiation.

Best wishes,

Georges

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