Tailoring tumor therapies
UCI doctor revives old tactic in hopes of sparing patients needless suffering by finding cancer drugs that suit them best.
THE ORANGE COUNTY REGISTER -- Saturday, July 12, 2003 By MAYRAV SAAR – The smartest approach to fighting cancer might just be ... to fight cancer.
Doctors at the American Association for Cancer Research conference in Washington, D.C., this weekend will hear about a new approach to an old and disparaged form of cancer treatment: customizing medicine directly to an individual tumor.
The idea is to target treatment directly to the tumor cells, often sparing healthy cells the worst of chemotherapy's damage. This is one of several approaches to "designer" therapies expected to be discussed at the conference. It highlights a push in oncology toward protecting patients against drugs and treatments that - though successful for some people - won't work for others.
Oncologists say they often prescribe patients one standard chemotherapy regimen after another, until they find the one that works. This can expose patients to the side effects of chemotherapy - hair loss, vomiting, weakness - without showing any cancer-killing results. Research led by Dr. Robert Nagourney of Long Beach Memorial Hospital suggests that the guesswork can be done in a laboratory instead.
"Once you've figured out what makes the cancer tick, it's a lot easier to kill it," said Nagourney, who is also an adjunct associate professor of pharmacology at the University of California, Irvine.
Nagourney's lab essentially takes pieces of tumor tissue, applies different chemotherapy treatments to it and examines the results to see which drug or combination of drugs does the best job killing the tumor cells. The tactic of using biopsied cells to predict which cancer treatments will work best for a patient is 30 years old. But Nagourney says those older tests failed because scientists looked to see which drugs inhibited the cancer cells' growth, not which chemotherapies actively killed the tumor cells.
"We had an erroneous understanding of cancer biology," Nagourney said. "Cancer isn't growing faster than other cells, it's just dying slower. We realized, 'Why don't we connect drugs to patients by what kills their cells, not by what slows them down?'"
Killing Cancer Kindly
This new twist of an old approach appears to be working. In a study published last year in the journal Gynecologic Oncology, for instance, a team of researchers tested how well women with relapsed ovarian cancer would respond to a combination of a pancreatic cancer drug and an ovarian cancer drug. They found the combination worked on a number of women, and that Nagourney's approach to testing cells in petri dishes predicted which women would respond to the drugs and which wouldn't.
"At first I was pretty skeptical, but we had patients who I thought were going to die, and suddenly they're walking into my office" months later, said Dr. Philip J. DiSaia, director of the division of gynecologic oncology at UCI, who participated in the ovarian cancer clinical trial.
"The other techniques haven't been terribly successful because they tell you which drugs are definitely not good. But this was a prediction of what would work," he said.
Mike Cook, 51, of Brea was diagnosed in January with metastatic pancreatic cancer, a disease that kills 96 percent of its victims. He was sure the diagnosis was a death sentence. A few months later, he was on the road to remission, hanging new windows in his home and taking vacations with his wife and kids. Nagourney is treating Cook with a combination of drugs commonly used to fight lung, pancreatic, breast and colorectal cancers.
'A rational therapy'
"I started to feel better almost immediately. I didn't have the throwing up, the hair loss," said Cook, who has had more than eight rounds of treatment. "It is taxing, but it's not nearly the image of chemotherapy we've all seen so many times. It feels like it's a rational therapy, and I'm not buckling under the strain of it."
Nagourney isn't the only researcher trying to find gentler, more targeted approaches to killing cancer. UCI urologist Dr. David Ornstein's work on proteomics, or the analysis of blood proteins, will also be presented at the AACR conference today. His work focused on detecting prostate cancer by looking at protein patterns in the blood.
Men who are suspected of having prostate cancer often undergo needle biopsies of their prostate to check for the disease. Researchers tested the blood of men who had had needle biopsies and found that the blood test could have saved 67 percent of the men who didn't have cancer from having to undergo the painful biopsy.
While this study focused on diagnosis, Ornstein said proteomics might also be used to predict which treatments would work for individual cancer patients. Researchers at the University of North Carolina have started a clinical trial to test the technology in finding fitting therapies for ovarian cancer patients.
"If you use targeted therapy, meaning you're only treating patients who will benefit from the treatments, you'll eliminate patients from having undue side effects without any benefit," Ornstein said. "The problem with standard chemotherapy is that it's like taking a machine gun and shooting everything in the way and hoping you get the cancer cells along with that."
While doctors seek the best way to match existing drugs to individual tumors, they also believe that emerging technologies will help find better, safer drugs to kill cancer.
Comparing current chemotherapy with the arsenic treatments once given for syphilis, Nagourney said, "Up until now, we've been indiscriminately poisoning healthy cells. Once you could identify a unique aspect to the (syphilis) bacteria, you could come up with penicillin," he said. "We are on the verge of developing penicillin for cancer.".
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