How does ADT work? Was: My Predicament

[Guest guest]

Charlie De wrote:

> Why does androgen deprivation therapy lower PSA levels? Does it

> kill the cancer cells or shrink them?

I did some reading on this question. It turns out that the

answer is ... Yes.

As near as I can tell, ADT both causes prostate cells to die and

also shrinks them and renders them less active.

One study found that the rate of tumor cell death increased 5.3

times with ADT as compared to no ADT.

The way I understand this is that most kinds of cells in our

bodies are in a continuous process of growth, replication by cell

division, and death. Not all cells divide and replicate, and not

all cells die, but tumor cells tend to do both. For a person

with a very aggressive cancer, the rate of cell replication is

high relative to the rate of cell death. For a person with

indolent cancer, the rate of cell division is equal to or only a

little higher than the rate of cell death.

As I understand it, ADT alters both sides of the equation with

prostate tumor cells. It reduces the rate of cell replication

and increases the rate of cell death. As a result, our tumors

shrink, our PSA levels go down, and if we have symptoms, the

symptoms decrease.

That's the outline. The details are incredibly complicated and

very, very incompletely understood (not just by me, but by the

experts too.) It appears that there are many different effects

of testosterone in healthy cells and tumor cells. It has been

found, for example, that blood flow to tumors decreases with ADT,

decreasing the nutrients needed to keep them alive. Certain

molecules that tell a cell to kill itself (a process called

" apoptosis " ) may increase in number under ADT, but how that

happens is still unclear. It may, for example, happen by

decreasing the production of certain other molecules that

suppress the chemical reaction that produce those apoptosis

promoting molecules.

I haven't done a lot of research on this, but among the articles

I found, the one that gave the most details was " Androgen

Deprivation Therapy for Prostate Cancer: Current Status and Future

Prospects " , by Hiroshi Miyamoto, M. Messing, and

Chawnshang Chang. It's available free on the Internet at the

following URL:

http://www.urmc.rochester.edu/george-whipple-lab/documents/miya-papers/19.pdf

It is *highly* technical. To fully understand it, you'll need a

fair amount of cell biology - understanding what a " gene " is and

does, " signal receptors " , " promoters " , " up and down regulation " ,

etc. But you may find some of it of interest even without

understanding all of that.

The article is already getting old. It was published in 2004.

But I haven't yet found anything on the Internat that is as

complete.

    Alan