How Prostate Cancers spread

[Paul Edwards]

With prostate cancer, traditionally it was thought that metastases formed as a result of cancer cells spreading from the primary tumour.

 

Two separate studies looking at how prostate cancers spread have just been published.  Both studies found evidence that cancer cells from metastases can migrate to other body parts and form new sites of spread on their own.

 

A science writer with the Cancer Research UK organisation has written an interesting article “Migration, settlement, and more migration: how prostate cancers spread” which looks at both these research studies.  You can read that article by clicking on this link.

 

The full text of one study “Tracking the origins and drivers of subclonal metastatic expansion in prostate cancer” can be found by clicking on this link.

 

This study looked at the direction and timing of metastatic spread.  They found that the cancer cells in some metastases had spread from earlier metastases, rather than from the primary tumour.  They found one case where a local recurrence in the prostate bed was seeded by a distant bony metastasis, rather than the other way around.

 

The researchers also observed that over time multiple waves of metastasis occurred from the primary tumour and suggested that surgical removal of the primary tumour might be warranted even from men with advanced cancer.

  

By ultra-deep sequencing of  blood samples, the researchers detected the presence in the blood of both metastatic and primary tumour clones, even years after removal of the prostate.

 

By clicking on this link, you can read a news report in Science Daily on the second study “The evolutionary history of lethal metastatic prostate cancer” .

[Bruce Kynaston]

It is good to see the level of research and its findings.

The earliest reference was dated 1976.

​In the early 60s I was taught that a mestatasis is capable of spreading cancer cells on to new sites.

A lymph mode deposit, as in the pelvis. will grow and send more cancer cells along the channels, eventually to reach the lungs. where deposits may send cells further afield through the arteries.

Alternatively, cells may enter the venules in the prostate and go to the lungs, or, when pelvic pressure is increased as in straining, pass into the bones about the pelvis.

Also, research at that time indicated that it would seem that single cells do not cause metastases as they can pass through the capillaries. (Venous blood taken from the elbow has blood that has been "filtered" by the lung capillaries and those of the hand and nearby tissues.

 

The library shelves can't carry all the old research, so 'the wheel gets reinvented', perhaps at a better level of science of course.

 

Fairly recent reports (one from Adelaide and a second from Melbourne) both showed that for a prostate cancer cell, to establish a metastasis, it must be accompanied by a noncancerous prostate stromal (support) cell. (Such a twosome could block a capillary to then implant and grow.

[Paul Edwards]

There's another article from Medscape about the second study mentioned in the original post.  It has an interesting comment from one of the researchers from the study:

 

 "One other finding from the study that has therapeutic implications is that the androgen-receptor pathway appears to be crucially important in prostate cancer.  'Each metastasis is different...and they become resistant in different ways to prostate cancer treatment,' Dr McDermott explained.  All of the patients had androgen-deprivation therapy and all became resistant to this treatment, but the sequencing showed that each metastasis became resistant in a different way (e.g., by amplifying the androgen receptor, or the receptor is mutated so the drug no longer works).  But while the mechanism of how they become resistant varied, all the mechanisms work towards the same goal of keeping the androgen pathway turned on."
" 'This is an important question in cancer: When the drugs stop working, is it because the cancer is now using a different pathway?  Well, this is telling us that, no, the cancer cells are working hard to keep this androgen pathway turned on, because this pathway is so important to cancer survival,' he said.  'This, in turn, suggests that working on drugs that block the androgen pathway is "the right way to go," and that second-generation androgen blockers may work even after initial androgen blockers stop working', he added. "