NICE GUYS CURE CANCER VALLEY RESIDENT DR. DENNIS SLAMON ELIMINATES DISEASE THROUGH INNOVATIVE GENE THERAPY.

Byline: Mariko Thompson Staff Writer

Dr. Dennis Slamon would seem to have every reason to be arrogant.

The longtime Valley resident is a celebrated UCLA scientist who pioneered a breakthrough breast cancer drug that opened the door for gene therapies targeting cancer cells while leaving healthy cells alone. His research is at the center of a high-powered fund-raising machine that sends the Hollywood elite scurrying for their checkbooks.

Yet he enters a room with the reassuring air of a small-town pediatrician who loves to make old-fashioned house calls. When others speak, he listens with undivided attention. He uses everyday analogies to explain the complexities of cancer research. He shows patience when asked to repeat - sometimes more than once - a scientific concept to a nonscientist. Had he chosen to return to his hometown of New Castle, Pa., he would have made a great family doctor.

``He's extremely humble,'' says Louise Cooper of West Hills, a friend who became a patient when she was diagnosed with breast cancer four years ago. ``I don't think he realizes the magnitude of his contribution. To him, this is what he does, and it's natural.''

Slamon, director of the Revlon/UCLA Women's Cancer Research Program at the UCLA Jonsson Comprehensive Cancer Center, was the driving force behind Herceptin, a drug that has proven effective against an aggressive type of breast cancer afflicting one in four women with the disease. The 54-year-old has received awards from his peers at the American Association for Cancer Research and from the National Breast Cancer Coalition.

While they may not know him by name, more than 60,000 Angelenos are expected to support his research efforts by participating in the annual Revlon Run/Walk for Women at the Coliseum on Saturday. The 5K event, along with the gala Fire and Ice Ball, have raised more than $25 million over the past 13 years for his program at UCLA.

``That's what broke this loose for us,'' says Slamon of the fund-raising events. ``If you're an investor in this research, we will make something happen with it. That's one of the things I feel best about. We've been able to make good on that promise.''

Beyond radiation and chemo 

The money didn't always flow so freely. In the scientific community, Slamon is known as an unconventional thinker. As a young cancer doctor with no track record in the early '80s, unconventional thinking didn't draw funding to his laboratory door. Breast cancer had not yet become a mainstream cause. Advocacy groups had not yet evolved into the great lobbying force for funding they are today.

Slamon arrived at UCLA in 1979 after completing medical school and a doctorate in cellular biology. At the time, strides had been made in treating certain types of cancer such as childhood leukemia, Hodgkin's disease and testicular cancer. But little headway had been made against the major cancers - lung, breast and colorectal. To scientists such as Slamon, who were dissatisfied with the pace of progress, it seemed clear the standard therapies of chemotherapy and radiation weren't leading to a cure.

Rather than bombard the body with chemo and radiation in the hope of killing more bad cells than good cells, Slamon and others began to seek ways to target just the bad cells. That meant figuring out what made the cell turn from normal to malignant in the first place.

``Pounding away with the guns that we had (then) didn't seem terribly rational to me,'' Slamon says. ``Why don't we go back to square one and figure out what's broken? In theory, we would have something that was at least as effective - if not more effective - but also less toxic.''

He and his team began looking at genes that regulated cell growth. About 40 or 50 had been identified at the time, compared to several hundred today. Genes that control cell growth can serve either as gas pedals or brakes, Slamon says. If either the gas pedal gets stuck or the brake fails, the cell experiences abnormal growth.

In 1986, Slamon became intrigued by a gene called HER-2, which operates as an antenna for the cell, receiving growth signals. Once broken, HER-2 becomes the stuck accelerator in the car analogy, feeding too much gas. The altered HER-2 gene appeared in about 25 percent of women with breast cancer. Worse, these women had terrible survival rates. The tumors did not respond well to traditional therapies, tended to metastasize quickly and had a high likelihood of recurrence.

Laboratory tests soon confirmed that the HER-2 alteration was the catalyst. Next his team began testing antibodies to counter the cell growth. They wanted an antibody to cover up the antennae and stifle growth.

Antibodies had not shown promise in previous studies. But Slamon was certain that was because the antibody didn't have a specific target. Using an antibody from the biotech company Genentech, Slamon's team was able to stop cell growth from the HER-2 alteration in the petri dish.

``Here's something that's ready for prime time,'' Slamon told himself.

Raising the stakes

Many patients and their families feel gratitude toward their doctors. Lilly Tartikoff was no exception. Tartikoff's husband Brandon, the former NBC executive who died in 1997 after battling Hodgkin's disease for more than 20 years, had become a patient of Slamon's in the early '80s. Slamon treated Brandon with cutting-edge drugs, which Tartikoff credits for extending her husband's life. Over the years, the Tartikoffs came to consider Slamon a close family friend.

In 1983, she offered to raise money for Slamon's research as a way of saying thanks. She had never raised money before but figured she could put her connections to use. Slamon declined. She persisted.

``Denny so stood apart from most doctors that I had encountered,'' she says. ``I had this feeling that between his obsessive passion and brilliance, he was going to come up with something. Some people seem charmed or special, and he was one of them.''

To friends, Slamon is just Denny, a guy who likes to fish, spend time with his two kids, and work in the yard of his Woodland Hills home. He hails from western Pennsylvania, a rugged region known for coal mining and producing great NFL quarterbacks. His wife, Donna, grew up in Butler, a town 30 miles away from his hometown of New Castle.

From an early age, Slamon knew he wanted to be a doctor. He noticed his parents' expressions of relief whenever Dr. Abraham Newmark came to the house to check on him or his two sisters.

``Kids can read their parents,'' Slamon recalls. ``It was like a huge weight was lifted. I thought, 'This guy has a pretty good job.' ''

Slamon describes Newmark as ``a really gentle soul.'' Slamon's patients say similar things about him. Cooper, now 49, was a neighbor of the Slamon family 20 years ago in Chatsworth.

``He is the most caring person,'' Cooper says. ``When I found the lump, I called him. I was desperate. What do I do? He arranged all of the appointments for me and took over.''

Herceptin won approval from the Food and Drug Administration in 1998 while she was undergoing chemotherapy. Tests showed Cooper had the HER-2 alteration. As soon as the drug was approved, Slamon made sure the elementary school teacher and adventure racer received the treatment, which is combined with chemotherapy. She took Herceptin intravenously once a week for a year.

``His confidence makes you feel confident,'' Tartikoff says. ``If there's a chance that anyone can help you, it's this man who knows so much about cancer.''

When she made the offer to raise funds, Tartikoff didn't care what kind of cancer Slamon was researching. She just wanted to help. In the late '80s, ready to go to clinical trial with the antibody that would be named Herceptin, he finally said, ``Yes.''

Shortcut to progress

Tartikoff went to Ronald Perelman, chairman of Revlon. Perelman was looking for a philanthropic cause that would help women. Tartikoff pitched Slamon's breast cancer research. Revlon provided $2.5 million to create the Revlon/UCLA Women's Cancer Research Program with Slamon at the head.

Without the private funding, the process would have been painstaking, Slamon says. Genentech supplied the antibodies. But trials entail other costs, including those for specialized equipment, clinical nurses and data managers. Slamon's lab operation runs about $1 million a year. A generous federal grant is about $200,000, he says.

``I can say unequivocally and absolutely we would not have Herceptin today,'' Slamon says. ``Would we have gotten to it eventually? Yes, probably in five or seven years or more.''

The first clinical trial to establish Herceptin's safety started in 1992. Women with advanced breast cancer received doses smaller than those given to a mouse. As doses increased, skin nodules that appear in advanced stages of the disease began to shrink.

In 1995, Slamon launched a large-scale study to compare Herceptin to the best available therapy at the time. The trial enrolled 450 women with breast cancer that had metastasized to other parts of the body. Response rate improved by 52 percent. The length of time the drug was able to control the disease improved by 65 percent. The relative risk of dying dropped by one-third.

``The most impressive thing in that final trial in the metastatic setting, we improved survival,'' Slamon says. ``That's something we hadn't been able to do in the preceding six decades.''

Slamon views study participants as partners and credits the courage of the women in the Herceptin trials.

``The real heroines of the story are the women who entered those studies,'' he says.

Today, two major tests are done on all breast cancer patients. One determines whether the cells are producing estrogen progesterone receptors, which will indicate whether hormone therapy might be effective. The other test is for the HER-2 alteration. While Herceptin does lengthen survival for a particularly deadly form of breast cancer, the greater accomplishment was showing how targeted gene therapy could work, says Dr. Christie Russell, co-director of USC's Lee Breast Center and president of the American Cancer Society's California division.

``Dr. Slamon's dogged efforts to prove the science behind this drug Herceptin allowed us to understand that this is a viable form of anti-cancer therapy,'' Russell says. ``It's an extremely promising area of research.''

The work on Herceptin continues. His UCLA team is 18 months into a trial looking at Herceptin's effect at the time of diagnosis, before the cancer has spread outside the breast. So far, the worldwide study has enrolled half of the 3,200 participants.

``The question is, if we add Herceptin right at the beginning, will it have an impact?'' Slamon asks. ``The answer we bet would be unequivocally yes. Now we have to prove that.''

REVLON RUN/WALK FOR WOMEN

What: Event to raise money for research on cancers affecting women. An estimated 54,000 women die each year from breast and ovarian cancer.

Beneficiaries: Revlon/UCLA Women's Cancer Research Program, National Women's Cancer Research Alliance, the Wellness Community, WIN Against Breast Cancer, the USC/Norris Comprehensive Cancer Center and more.

Where: Los Angeles Memorial Coliseum.

When: Saturday. Check-in begins at 7 a.m., opening ceremonies at 8 a.m.

Registration: $30. Call [phone] or visit www.revlonrunwalk.com

CAPTION(S):

4 photos

Photo:

(1 -- cover -- color) Humble warrior

The modest - even folksy - Dr. Dennis Slamon of UCLA pulls no punches when it comes to fighting breast cancer

(2) no caption (Dr. Dennis Slamon)

(3) UCLA researcher Dr. Dennis Slamon, whose work on the drug Herceptin has helped revolutionize breast-cancer treatment, discusses a project with scientist Juliana Oh at UCLA's Jonsson Cancer Center.

(4) Dr. Dennis Slamon and daughter Joey at the starting line of the Revlon Run/Walk for Women. This year's fund-raising event takes place Saturday at the Los Angeles Memorial Coliseum.

Michael Owen Baker/Staff Photographer