Prostate Adventures: Another Reason to Appreciate the California Stem Cell Program

Cancer is tough to kill. It may go into remission and come back later. Fortunately, the California stem cell program is pretty tough too.
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"Scoot your bottom over," said the nurse as I lay on my side in the backless hospital gown.

I felt a sudden inclination to resist. Maybe if I just said no, got up and put my clothes on, I could walk out of there, and life would go back to normal.

But the moment passed. I did as requested, and the Roto-Rooter sample takers invaded, taking 12 little chunks out of me. If that sounds gross and terrifying (and mildly painful), you have an accurate assessment of the situation.

The test results came back, and an appointment was set up -- immediately.

"You have cancer," the doctor said by way of greeting.

Since an estimated 90 percent of all males get prostate cancer if they live long enough, I was not immediately concerned. But when he mentioned some actual numbers, he had my undivided attention.

This year, roughly 240,000 male Americans will be diagnosed with prostate cancer, and 30,000 will die of it.

Because prostate cancer is generally slow-growing, many don't know they have it, and they die of old age; the cancer was there, but it just did not give them problems.

But for some, the cancer must be dealt with. One important measuring device is called the Gleason score, which ranges from 1 (no problem) to 10 (the worst).

With my score of 7, some form of action was required. Options included surgery to remove the offending prostate gland, or radiation, hormone therapy, or possibly even chemotherapy, or some combination thereof.

I went with the surgery, a "radical prostatectomy," and a little robot did the cutting.

It was a nightmare with moments of comedy. My wedding ring had to come off before the surgery, and when I woke up, my first words came out in a squeaky Elmer Fudd "you wascally wabbit" kind of voice: "Where is my wedding 'wing'?" There were also some hopefully temporary side effects, like incontinence, etc.

When the prostate was dissected, it showed a more aggressive cancer than they'd hoped to find: On the Gleason scale it was an 8 instead of a 7.

Best-case scenario? Hopefully the cancer is gone, removed with the prostate gland.

But if the cancer has spread, I will probably need radiation therapy. This is not fun: six weeks of daily sessions, with such possible side effects as rectal cancer.

If I need it, the highly targeted radiation should kill most of the cancer, maybe enough to keep me healthy for five, 10, 15 years or more. It's hard to tell.

Cancer is tough to kill. It may go into remission and come back later.

Fortunately, the California stem cell program is pretty tough too.

The California Institute for Regenerative Medicine (CIRM) has several projects that have suddenly become of great interest to me.

One is pioneering Stanford scientist Dr. Irv Weissman's work, which I wrote about previously.

Another, led by Dr. Owen Witte of UCLA, involves signals that turn cancer on -- and, hopefully, off.

To say Witte is a qualified researcher is like saying Mount Everest is a decent-sized hill. The author or co-author of 363 published papers, Dr. Witte is the director of the Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research.

If I were to list all his awards, accomplishments and responsibilities, there would be no room for the blog post.

The research that may one day save lives or ease suffering? Let's take a look.

With a CIRM Basic Biology IV grant (#RB4-06209) of $1,254,960, Dr. Witte is studying the pathways of cancer.

Do you know how the male hippopotamus fights? The giant water mammals come up on dry land and charge each other on paths worn down by their bodies, crashing together. The winners get to mate, so they fight hard -- but they do not kill each other. When one loses, it just leaves the pathway.

Dr. Witte identified "important signaling pathways that regulate (the) growth of normal prostate tissue stem cells ... Human cancers utilize these same pathways to promote malignancy and ... tumor progression."

When cancer comes, it "dysregulates" the pathways.

How to stop the cancer and let the good stem cells control the pathways?

Our recent studies have uncovered an important ... molecule (Trop 2) that is expressed on ... prostate cancer cells ... [It] is selected for ... advanced disease and predicts poor prognosis for many tumors including prostate, ovarian, pancreatic, breast, gastric and colorectal cancer.

Dr. Witte gave me a highly scientific explanation of how Trop 2 activates cancer, which I will share in a moment.

But I understand it like a video game my granddaughter plays, which I call "Fruits and Bombs." On the screen pop up a bunch of watermelons, pineapples, grapes -- and cartoon bombs. You run your fingers across the screen, slashing the fruits, but if you touch a bomb, it explodes, and you lose.

For Trop 2 to activate the cancer, it has to be slashed (cleavage) by enzymes called proteases. If we can prevent the slashing, we might also block the cancer.

Now, for the scientists in the audience, here are Dr. Witte's words.

Trop 2 requires cleavage ... to activate its growth-promoting (including cancer-causing--DR) properties.

Trop 2 is a molecule that crosses the cell membrane. ... To send its growth signal, a sequence of cuts have to be done on the molecule. These are carried out by enzymes called proteases. One is located outside the cell and it cuts first. Then a second protease cuts inside the cell and a fragment of the Trop 2 moves to the nucleus and signals for growth ... (personal communication)

Our goal is to use very specific antibody molecules to block the first protease cleavage event on Trop 2 ...

[Therefore] ... we are generating antibodies that will block Trop 2 activation ... We predict that blocking Trop 2 ... will be an effective strategy to prevent disease progression in prostate and other human cancers....

Dr. Witte points to the pressing need for better cancer treatments, saying:

[Currently] advanced stages of prostate cancer are treated with hormonal therapy, which causes significant changes in mood, body weight and composition, impotence and gynecomastia [men growing breasts], in addition to the pain and suffering from the disease....

His goal? "[T]o significantly extend life and minimize suffering of men with advanced prostate cancer."

And he adds, "Many of the molecules that we are investigating are implicated in a range of tumors, suggesting that our findings may provide benefit to patients suffering from numerous cancers."

With determination, intelligence, and passion, CIRM scientists like Owen Witte fight to solve diseases like prostate cancer -- which potentially threatens every male on the planet.

Is it any wonder I consider the California stem cell program to be the pride of our state, the glory of our nation, and a friend to all the world?

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