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LB doctor challenges status quo of cancer treatments

September 27th, 2007 · 1 Comment · Health, News

nagourney.jpgBy Nick Diamantides, Staff Writer

Robert Nagourney, MD, has developed a technique for treating cancer patients that has one of the highest success rates in the world, but so far, most of the medical establishment is ignoring his discoveries.
In addition to being the medical director of the Malcolm C. Todd Cancer Center at Memorial Medical Center of Long Beach, Nagourney is medical and laboratory director at Rational Therapeutics, Inc., (across the street from Memorial) and adjunct associate professor of pharmacology at the University of California, Irvine.
“I’m not some fly-by-night investigator,” he said, explaining that several years ago he decided to go back to the drawing board and figure out why modern therapies are not more effective at saving or at least prolonging the lives of cancer patients. Nagourney stressed that his technique does not rely on experimental cancer drugs.
“We only use FDA-approved cancer drugs,” he said. “What we do differently is conduct a laboratory process to determine which drug or combination of drugs will work best for the patient before administering them.”
The doctor explained that about 15 years ago, while attending a lecture given by Nobel Prize winner Robert Horvitz, he changed his thinking on cancer.
According to Nagourney, most doctors and scientists will say that cancer cells divide rapidly and grow without any control, but the way he looks at it, cancer is actually a disease of cells that don’t die. “The regulatory process that is out of whack is really the (cancer cell) death rate, not the growth rate,” he said.
With that change in focus, Nagourney began seeking more efficient ways to kill the cancer cells within patients’ bodies.
“I can easily measure cancer behavior in a test tube if all I need to do is kill it,” he said. “But it becomes rather difficult to grow cancer cells and make them behave the way they should behave in a patient.”
Modern cancer drugs are developed and tested in laboratories – first in test tubes and then in mice or other animals. After that, they are tested in humans. If a drug has a favorable response rate in humans, it will often get FDA approval even if the response rate is as low as 15 percent. A favorable response rate, however, does not always mean that a patient is cured. It may simply mean that the drug slows down the cancer’s progress or causes it to temporarily go into remission. Even those favorable effects, however, may only be experienced by 15 percent of the patients using a particular drug.
Nagourney said billions of dollars are spent each year to administer cancer drugs with very low response rates. He opened Rational Therapeutics in 1993 in hopes of changing that scenario and prolonging the lives of cancer patients.
The laboratory uses tissue samples from the patient to create “platforms” in which the cancer cells live. “As far as the cancer is concerned, it’s still living inside the patient,” Nagourney explained. “We then expose it to drugs that we might consider giving the patient.”
He noted that if he can find a drug that causes the cancer cells to die in the patient’s tissue samples, that drug (or combination of drugs) would likely have the same effect in the patient’s body.
Following that procedure has led to astounding results, according to Nagourney. “Our current objective response rate in colon cancer is 88 percent and in non-small cell lung cancer it’s about 65 percent,” he said. “That’s neatly double the clinical outcomes in the best institutions in the world.”
Nagourney does not provide treatments for cancer, however. Rather, he oversees the laboratory procedure and them recommends the drugs his tests show to be the most effective.
“On a percentage basis, two or three times more patients get better in my care than in anybody else’s care,” he said. “I have the documents to prove we are doing a better job than the best cancer treatment centers in the world.”
The doctor lamented that in spite of his lab’s success rate, the American medical establishment has not yet accepted his procedure and simply continues selecting cancer therapies that have the highest response rates.
“The problem with most of the academic community is that they don’t gladly change their approach,” he said. “Paradigm shifts are uncomfortable.”
Nagourney said that in order for his procedure to win wide acceptance it will have to undergo extensive clinical trials conducted by a recognized medical research institution, but so far none of them have been willing to conduct the trials.
He added that he is astonished that most insurance companies have also not yet accepted the validity of his lab procedures, and have thus forced many of his patients to pay for the work out of their own pockets.
“I guarantee that we have a process that matches treatments to patients and results in favorable outcomes,” he said. “That process should be in place today anywhere cancer patients are being treated. The mathematics are so in our favor that it is astonishing that people aren’t doing this more.”
He noted, however, that Memorial Medical Center is supporting clinical trials that test the ability to improve outcomes in certain types of cancers. Some insurance companies are also seriously considering paying for the lab work he provides.
Rational Therapeutics is located at 750 East 29th Street in Long Beach.
For more information, phone (562) 989-6455 or visit www.rationaltherapeutics.com

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One Comment so far ↓

  • gpawelski

    Personalized Cancer Medicine Is Here, NOW!
    As we enter the era of “personalized” medicine, it is time to take a fresh look at how we evaluate treatments for cancer patients. More emphasis is needed matching treatment to the patient. Patients would certainly have a better chance of success had their cancer been chemo-sensitive rather than chemo-resistant, where it is more apparent that chemotherapy improves the survival of patients, and where identifying the most effective chemotherapy would be more likely to improve survival.

    Findings presented at the 41st Annual Meeting of the European Society for Clinical Investigation in Uppsala, Sweden and the Annual Meeting of the American Assoication for Cancer Research (AACR) in San Diego, CA concluded that “functional profiling” with cell-based assays is relevant for the study of both “conventional” and “targeted” anti-neoplastic drug agents (anti-tumor and anti-angiogenic activity) in primary cultures of “fresh” human tumors.

    Cell-based Assays with “cell-death” endpoints can show disease-specific drug activity, are useful clinical and research tools for “conventional” and “targeted” drugs, and provide unique information complementary to that provided by “molecular” tests. There have been more than 25 peer-reviewed publications showing significant correlations between cell-death assay results and patient response and survival.

    Many patients are treated not only with a “targeted” therapy drug like Tarceva, Avastin, or Iressa, but with a combination of chemotherapy drugs. Therefore, existing DNA or RNA sequences or expression of individual proteins often examine only one compenent of a much larger, interactive process. The oncologist might need to administer several chemotherapy drugs at varying doses because tumor cells express survival factors with a wide degree of individual cell variability.

    There is a tactic of using biopsied cells to predict which cancer treatments will work best for the patient, by taking pieces of live “fresh” tumor tissue, applying different chemotherapy treatments to it, and examining the results to see which drug or combination of drugs does the best job killing the tumor cells. A cell-based assay test with “functional profiling,” using a cell-death endpoint, can help see what treatments will not have the best opportunity of being successful (resistant) and identify drugs that have the best opportunity of being successful (sensitive).

    Funtional profiling measures the response of the tumor cells to drug exposure. Following this exposure, they measure both cell metabolism and cell morphology. The integrated effect of the drugs on the whole cell, resulting in a cellular response to the drug, measuring the interaction of the entire genome. No matter which genes are being affected, functional profiling is measuring them through the surrogate of measuring if the cell is alive or dead.

    For example, the epidermal growth factor receptor (EGFR) is a protein on the surface of a cell. EGFR-inhibiting drugs certainly do target specific genes, but even knowing what genes the drugs target doesn’t tell you the whole story. Both Iressa and Tarceva target EGFR protein-tyrosine kinases. But all the EGFR mutation or amplificaton studies can tell us is whether or not the cells are potentially susceptible to this mechanism of attack. They don’t tell you if Iressa is better or worse than Tarceva or other drugs which may target this. There are differences. The drugs have to get inside the cells in order to target anything. So, in different tumors, either Iressa or Tarceva might get in better or worse than the other. And the drugs may also be inactivated at different rates, also contributing to sensitivity versus resistance.

    As an example of this testing, researchers have tested how well a pancreatic cancer patient can be treated successfully with a combination of drugs commonly used to fight lung, pancreatic, breast, and colorectal cancers. The pre-test can report prospectively to a physician specifically which chemotherapy agent would benefit a cancer patient. Drug sensitivity profiles differ significantly among cancer patients even when diagnosed with the same cancer.

    The funtional profiling technique makes the statistically significant association between prospectively reported test results and patient survival. It can correlate test results that are obtained in the lab and reported to physicians prior to patient treatment, with significantly longer or shorter overall patient survival depending upon whether the drug was found to be effective or ineffective at killing the patient’s tumor cells in the laboratory.

    This could help solve the problem of knowing which patients can tolerate costly new treatments and their harmful side effects. These “smart” drugs are a really exciting element of cancer medicine, but do not work for everyone, and a pre-test to determine the efficacy of these drugs in a patient could be the first crucial step in personalizing treatment to the individual.

    Literature Citation:
    Functional profiling with cell culture-based assays for kinase and anti-angiogenic agents Eur J Clin Invest 37 (suppl. 1):60, 2007
    Functional Profiling of Human Tumors in Primary Culture: A Platform for Drug Discovery and Therapy Selection (AACR: Apr 2008-AB-1546)

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