A New Tool for Battling Prostate Cancer

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Ken S
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Date Joined Nov 2006
Total Posts : 120
   Posted 4/7/2009 7:51 PM (GMT -6)   
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Smart weapon. A new compound that gums up the androgen receptor shrank drug-resistant prostate cancer tumors in mice (lower row, tumors after 5 days).

Credit: C. Tran et al., Science

A New Tool for Battling Prostate Cancer

By Jocelyn Kaiser
ScienceNOW Daily News
7 April 2009

For the unlucky 10% of men diagnosed with prostate cancer who have the most aggressive form, the prognosis is grim. The available prostate cancer drugs may initially shrink their tumors, but the remaining cancer cells usually grow out of control again after a couple of years. These drug-resistant cases account for most of the nearly 29,000 annual deaths in the United States from prostate cancer.

Researchers led by Charles Sawyers at Memorial Sloan-Kettering Cancer Center in New York City have now developed a compound that could prevent some of the deaths. This Thursday, they will report online in Science that in mice the compound shrank implanted human prostate tumors untreatable with current drugs and that it showed signs of arresting tumor growth in men with similarly drug-resistant cancer. Although more clinical studies are needed, cancer researchers are excited about the potential drug, which tackles prostate cancer by a mechanism different from that of current drugs. "It's possibly a new and better way of treating prostate cancer," says oncologist Philip Kantoff of the Dana-Farber Cancer Institute in Boston.

In prostate cancer, genetic changes within cells allow testosterone and similar hormones, known as androgens, to fuel unrestrained cell growth. Most patients receive drugs to limit the body's production of androgens. If the tumor continues to grow, physicians prescribe other drugs that bind to the androgen receptor in the prostate cell's cytoplasm so that the hormone cannot land on the receptor and turn it on. But these drugs usually fail after a time.

This problem intrigued Sawyers, who had earlier worked on resistance to Gleevec, a potent leukemia drug he helped develop. In 2003, Sawyers's team showed why cells from advanced prostate tumors eventually thwart standard drugs: The cells produce high levels of the androgen receptor, and this makes them so sensitive to androgens that even the receptor-blocking drugs can stimulate the cells to grow. Sawyers next joined forces with chemist Michael Jung, whose group at the University of California, Los Angeles, synthesized nearly 200 androgen-like compounds. The researchers screened the molecules, selecting ones that bound tightly to the androgen receptor but didn't activate it. Jung's group then tweaked promising candidates to make two potential drugs.

In addition to binding to the androgen receptor, the new compounds seem to hinder it from getting into the cell's nucleus, binding to DNA, and triggering the expression of genes, the team reports. "It's a beautiful story," says cancer pharmacologist Donald McDonnell of Duke University in Durham, North Carolina.

In a clinical study with one of the compounds, dubbed MDV3100, levels of prostate-specific antigen--a marker for prostate tumor growth--dropped by at least 50% in 13 of 30 patients with advanced disease for whom other treatments had failed. "For this group of patients, this is a very impressive result," says Sawyers. Medivation Inc. in San Francisco, California, which collaborated on this work, is now testing the drug at higher doses on more patients. (Sawyers is a consultant for the company and is a co-inventor on a patent for MDV3100.)

Even if MDV3100 extends the lives of men with advanced prostate cancer, their tumors will likely become resistant to it, too. But researchers hope the compound can be combined with another drug candidate, developed by a different team but also in trials, that stops cancer cells from making their own supply of androgens. "A very exciting possibility" is that a cocktail of these drugs will prevent men with early prostate cancer from ever reaching the drug-resistant stage, says Kantoff, who heads one of several centers that are testing MDV3100.

Age 54 (2006)
PSA: 2005 - 3.2, 2006 - 3.7
Biopsy 8/06, Gleason 6 (3+3), T1c
Radical Retropubic Prostatectomy 11/3/06 - Memorial Hospital, Pawtucket, RI
Post-Op Biopsy, Gleason 6 (3+3), T2c, right apical margin positive
CT Scan 1/07, tumor discovered on right kidney (unrelated to PCa)
Partial Nephrectomy 3/9/07 - R.I. Hospital, Providence, RI
IMRT (37 Treatments) 4/23/07 - 6/14/07
PSA: 3/09 - 0.03

Regular Member

Date Joined Sep 2008
Total Posts : 143
   Posted 4/8/2009 11:22 AM (GMT -6)   

Thanks for the post! There are several encouraging initiatives out there that bring us hope this beast will soon be tamed.

Bill in SD

Age 60 (59 when Dx) PSA 4.4
Biopsy 5/15/08 Gleason (3+3=6)
Bone scan and pelvic CT: clear
HT - 2 mo Casodex, 3 mo Trelstar
RRP Surgery 9/15/08 La Mesa California
Post-OP Gleason 3+4=7, Stage pT2c pN0 MX
Seminal vesicals, perineural margin, 18 lymph nodes, bladder neck: all carcinoma free
Perineural invasion & Distal Margin: Carcinoma present
IMRT adjuvant radiation (35 Treatments) End 1/27/09
PSA (10/13/08): <0.1
PSA (3/13/09): <0.1

Regular Member

Date Joined Jan 2009
Total Posts : 32
   Posted 4/8/2009 12:57 PM (GMT -6)   
Thanks Ken! Very is exciting information.
Age 59, very healthy
Psa 2007 3.2
Psa fall 2008 4.9 two weeks later 4.4
11/2008 biopsy, T1c, gleason 3+3=6 low-volume prostrate carcinoma
1 of 12 samples malignant
Left lateral mid .05mm (5%)
CT scan negative
Consultation 12/2008 decided active waiting (diet) while researching options.
Followup PSA in March 2009
PSA March 2009 3.5!

Veteran Member

Date Joined Apr 2008
Total Posts : 1382
   Posted 4/9/2009 4:39 PM (GMT -6)   
This is exciting news. The most encouraging thing is that something is being done. I love it when I hear about research in the cure and treatment of PCa.
Thanks for the post

peace and grace
My PSA at diagnosis was 16.3
age 46 (current)
My gleason score from prostate was 4+5=9 and from the lymph nodes was 4+4=8
I had 44 IMRT's
Currently on Lupron
I go to The Cancer Treatment Center of America
Married with two kids
latest PSA 5-27-08 0.11
PSA July 24th, 2008 is 0.04
PSA Dec 16th, 2008 is .016
PSA Mar 30th, 2009 is .02
Testosterone keeps rising, the current number is 156, up from 57 in May
T level dropped to 37 Mar 30th, 2009
cancer in 4 of 6 cores

Regular Member

Date Joined Dec 2008
Total Posts : 194
   Posted 4/9/2009 5:06 PM (GMT -6)   
That is a great article Ken. And very encouraging. Thanks for finding and posting it.
Age at DX 57
5-18-07 PSA 7.7
5-06-08 PSA 4.6  8% free psa, but stable
10-23-08 PSA 5.65 4% free psa
11-04-08 biopsy
11-11-08 2 of 12 cores positive
Gleason 3+3  6  stage t1c / post-op 3+4  7  stage t2c
CT and Bone scan negative
Da Vinci RRP 01-09-09
Catheter removed 1-15-09
Pathology Report says it's gone!
First Post-op PSA 2-17-09   0.00

Veteran Member

Date Joined Jul 2008
Total Posts : 637
   Posted 4/10/2009 2:20 PM (GMT -6)   
I was thrilled to read this article...Thank you very much Ken. Our oncologist is at MSK and I will certainly bring up this article to him. I am amazed that sometimes physicians in the same hospital do not have the same information.... We all really need to take charge of our own health issues.... Thanks again for this very good news. Diane
Husband Pete
dx Jan 2001 gleason 4 + 3 PSA 16.5
Seed implant and conformal radiation and Lupron from Jan 2001 to Jan2002
2005 Dec PSA began to rise from .5 to 8 within 6 months
Salvage surgery at MSK 9/06 Dr. Eastham
Fistula operation 2/07 MSK Dr. Wong
Many cystoscopies and ER visits with strictures
Catheter for one year....Catheter taken out Sept 07..
Total Incontinence since then....
PSA .52 3/08
AUS Operation at MSK Sept 8 2008 Dr. Sandhu
Activated Oct 28th Dr. Sandhu..MSK
Some difficulty with AUS arising Nov 10 2008
Meeting with Dr. Sandhu to discuss AUS problems and new PSA test Dec 11, 2008
PSA .6 12/08
AUS improving..only 2 pads a day and one at night
Complete hip replacement surgery Dr. Waters Gainesville, FL 1/9/09
Hip replacement total success..pain gone!!
PSA .7 2/10/09

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