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Science Makes Inroads Against Prostate, Other Cancers
Date:4/19/2009

In studies, an immune boost fights prostate tumors, and better drugs outwit brain, pancreatic malignancies

SUNDAY, April 19 (HealthDay News) -- Harnessing cutting-edge techniques, a variety of human, animal and laboratory studies are suggesting innovative new ways to beat cancer.

Brain, prostate, and pancreatic cancer are some of the specific targets of the new research described Sunday in Denver at the annual meeting of the American Association for Cancer Research.

"This is an extremely exciting time in cancer research," observed Dr. David Carbone, director of the thoracic oncology center at the Vanderbilt-Ingram Cancer Center in Nashville. "Even in the kinds of cancers that traditionally have been very resistant to therapy, we're starting to see clues of amazing responses and clinical benefits for patients."

Carbone, himself a cancer survivor, was not engaged in any of the investigations under discussion in Denver.

One of the studies involved a clinical trial into a new therapy for prostate cancer. That study's lead author, Dr. Richard Junghans, described his team's effort as an attempt "to find a cure for patients who will ultimately die, because standard therapies don't really work".

"Prostate cancer kills about 3,000 [men] every month," observed Junghans, an associate professor in the department of surgery and medicine at Boston University School of Medicine, as well as chief of the division of surgical research at Roger Williams Medical Center in Providence, R.I. "Chemotherapy doesn't work, and hormone treatment can keep the prostate under control for one to two and maybe even three years. But after that, there's very little left. So almost all patients who've had their cancer spread to the bones will die, and it can be a miserable way to go."

"So, what we've done is to go in a radical new direction to develop a therapy that is not a chemical, not an inert drug, not a hormone," he explained. "It's almost a living organism. It's actually the patient's own T-cells -- white blood cells that exist in everyone's body -- that have been modified and engineered to be 'fooled' into attacking the cancer."

Junghans said that the first two patients to receive a single infusion with the new treatment experienced a 50 percent to 75 percent reduction in their blood level of prostate-specific antigen (PSA), a measure of prostate cancer activity, over the following two months.

"So, I'm very excited, because this achievement was with the lowest dose of the therapy, which we now plan to try out at a level ten times as high," he noted. Junghans said he and his team hope to "achieve a 100 percent reduction (in PSA)."

Another of the four studies included work led by Florence Hofman, a professor of pathology at the University of Southern California, Keck School of Medicine, in Los Angeles. Her team targeted brain cancer with an inhibitor called "dimethyl-celecoxib".

Celecoxib may sound familiar: It's the more scientific name for the cox-2 inhibitor drug, Celebrex, which has been used as a pain reliever and cancer-fighter but also has some cardiovascular side effects. The new drug is "similar to a cox-2, but not quite the same," Hofman noted. "It's like a key in a lock. You just change one of the little teeth in the key -- a molecule for example -- and it does one thing but not another, even if it looks very much the same. So then, we get the very great advantage of avoiding some known and dangerous side effects."

The therapy appears to inhibit new blood vessel growth as part of its strong anti-tumor effect, Hofman said. Specifically, in animal studies, this cox-2-like agent achieved a 35 percent to 45 percent reduction in the density of tumor blood vessels without the development of any potentially damaging long-term side effects.

Hofman and her colleagues noted that though their current focus was on brain cancer, the therapy could have applications for other types of cancer, including breast cancer.

However, "this is not a wonder-drug," Hofman cautioned. "We don't have a cure for cancer here. But the approach we've taken and tested in lab and with rodent models looks very promising for future therapy with brain tumors."

Another study, led by researchers at the Mayo Clinic in Rochester, Minn., looked at inhibiting pancreatic cancer at the cellular level with a combination of two new agents: a histone deacetylase inhibitor called LBH589 and a mTOR inhibitor called rapamycin.

When used together, the two drugs appeared to provide more anti-cancer punch than they would have singly, the team said. While treatment with rapamycin alone only resulted in a tumor cell death rate of about 10 percent, the two drugs in combination elicited a 60 percent to 70 percent death rate. Any improvement in outcomes is welcome for patients battling pancreatic cancer, a malignancy that, because it is often detected late, has a very high mortality.

A fourth study was conducted by the biotech company Genentech. Researchers there honed in on specific proteins generated by a key player in cancer development, known as the "ras" oncogene.

In lab work, the study authors found evidence that by interrupting the pathways by which these proteins signal and trigger tumor growth, they were able to produce "significant" tumor cell death.

At this point in cancer research, "we obviously have a long way to go," remarked Vanderbilt's Carbone. "But this is all about more than just hope. I've been practicing for 18 years now, and I can say that we now are developing a new reality, as we learn more and more about cancer. And this will translate into real people having real responses and real improvements in their quality of life as they battle cancer. And that is what's so exciting."

More information

There's more on the effort to beat cancer at the American Association for Cancer Research.



SOURCES: Richard Junghans, Ph.D., M.D., associate professor, department of surgery and medicine, Boston University School of Medicine, and chief, division of surgical research, Roger Williams Medical Center, Providence, R.I.; Dr. David Carbone, M.D., Ph.D., director, thoracic oncology center, Vanderbilt-Ingram Cancer Center, Nashville, Tenn.; Florence Hofman, Ph.D., professor of pathology, University of Southern California, Keck School of Medicine, Los Angeles; presentations, April 19, 2009, American Association for Cancer Research annual meeting, Denver


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