Clinical Cancer Research: Improving Detection, Treatment and Prevention


Washington University School of Medicine in St. Louis

Joni Westerhouse

Barnes-Jewish Hospital, Member BJC HealthCare
Jason Merrill

Aug. 15, 2001 – The Alvin J. Siteman Cancer Center advances the state of medical science by supporting research aimed to help current and future generations of cancer patients conquer their disease. In 2000, Siteman Cancer Center had 640 active clinical research studies including 386 clinical trials. More than 3,500 people enrolled in cancer detection and prevention trials affiliated with Siteman. More than 600 others participated in cancer therapy studies. Researchers investigate every kind of cancer with studies ranging from prevention and early detection to treatment for patients with advance forms of disease as highlighted in the following examples.

Breast cancer vaccine
Researchers at Siteman Cancer Center are working on vaccines for metastatic breast cancer. Timothy J. Eberlein, M.D., Paula M. Fracasso, M.D., Ph.D., and David Linehan, M.D., developed one potential vaccine, which causes the body's immune system to recognize as foreign part of a protein produced at high levels in about one-quarter of women with breast cancer. The protein called HER2/neu, revs up the growth of breast cancer cells, making the cancer harder to control. The investigators have begun a clinical study to determine if the vaccine can extend a woman's life by inducing her body to attack the cancerous cells. Eberlein is director of the Siteman Cancer Center and Spencer T. and Ann W. Olin Distinguished Professor at Washington University School of Medicine. He also serves as surgeon-in-chief at Barnes-Jewish Hospital. Fracasso is associate professor of medicine, School of Medicine, and Linehan is assistant professor of surgery, School of Medicine

New radiation therapy technique
Patients with head and neck cancers are benefiting from a cutting-edge radiation technique called intensity modulated radiation therapy (IMRT). K.S. Clifford Chao, M.D., and other radiologists at Siteman Cancer Center are among the few researchers nationwide who are studying the use of IMRT. As an emerging technique, IMRT precisely targets tumor cells while sparing surrounding normal tissue. This means, for example, nerves to the eyes and brain are less likely to receive unintended radiation during treatment of cancer of the nasal passages. IMRT also means the tumor gets a higher concentration of radiation than it would with conventional techniques. Chao showed that IMRT minimizes damage to salivary glands, sparing patients the long-term discomfort of dry mouth. Patients receiving conventional radiation for head and neck cancers often suffer from this side effect, which causes constant thirst and inability to speak or eat normally. Chao is assistant professor of radiology at the medical school's Department of Radiation Oncology.

Preventing breast cancer
Siteman Cancer Center is participating in the Study of Tamoxifen and Raloxifene (STAR) trial, one of the largest breast cancer prevention studies ever. Nationwide, the trial will include 22,000 postmenopausal women at increased risk for breast cancer to determine whether the osteoporosis prevention drug raloxifene (Evista) is as effective in reducing the chance of developing breast cancer as tamoxifen (Nolvadex). Joanne E. Mortimer, M.D., professor of medicine and director of clinical oncology in the Division of Medical and Molecular Oncology at the School of Medicine, is heading the effort.

Brain tumor imaging
To assess the severity of a brain tumor, Benjamin C. P. Lee, M.B.B.S., is performing early clinical trials to evaluate the use of a non-invasive imaging method for revealing how many veins a tumor has. Because veins carry waste products away from a tumor, they can indirectly suggest how aggressive a tumor might be, which could guide treatment selection. The high resolution BOLD venography method, which highlights low concentrations of oxygen in veins and capillaries, also could help doctors decide the regions within a tumor to biopsy, or provide a way to assess the effect of drugs that destroy the blood vessels feeding a tumor. Lee is associate professor of radiology and pediatrics at the School of Medicine and a diagnostic radiologist at St. Louis Children's Hospital.

Early cancer detection
To determine whether screening for certain cancers saves lives, Gerald Andriold, M.D., is principal investigator of the St. Louis portion of a national cancer screening trial. The Washington University study is based at Barnes-Jewish West County Hospital and tests for cancers of the prostate, lung, colon and ovaries. Called PLCO, the study is recruiting volunteers with no known cancers. Some receive free cancer screening tests, while others continue with their usual medical care. Andriole is professor of surgery and director of the Division of Urologic Surgery at the School of Medicine. He is also director of the Urologic Research Center at Barnes-Jewish West County Hospital, where he conducts cancer prevention trials.

Chemotherapy for breast cancer
Understanding how chemotherapy affects tumors-and why it sometimes does not-can affect treatment recommendations for cancer patients, David R. Piwnica-Worms, M.D., Ph.D., is studying a protein on the surface of cancerous cells that allows them to spit out chemotherapeutic drugs. Cells lacking the protein, called p-glycoprotein, cannot rid themselves of drugs or a radioactive compount that can be imaged using a technique called single photon emission computed tomography, or SPECT. For this reason, Piwnica-Worms is determining in an early clinical trial whether women with breast cancer take up the imaging compound in their tumors, suggesting that they are good candidates for chemotherapy. He is professor of radiology and of molecular biology and pharmacology at the School of Medicine.

Understanding nicotine dependence
Investigators at the Siteman Cancer Center are participating in national and international efforts to determine the factors influencing nicotine dependence. These studies are providing provocative evidence that although there are important environmental influences on who first becomes a smoker, once regular smoking has developed, genetic factors become much more important in predicting difficulty quitting smoking. The framework for much of the research on cigarette-related behavior comes from studies of twins. One of the largest twin studies to date comes from research published recently by Pamela A.F. Madden, Ph.D., assistant professor of psychology, and Andrew C. Heath, Ph.D., professor of psychology. The investigators from the psychiatry department studied the smoking behavior of more than 20,000 pairs of same-sexed, identical and non-identical twins from Australia, Sweden and Finland. By analyzing the responses to health surveys, the investigators were able to suggest that genes had a different impact on two steps in the process of nicotine dependence. Early smoking experiences seemed to be influenced more by environmental factors that were shared by both twins. But genetics was more crucial once regular smoking began. Another team of investigators has taken a different approach. Theodore Reich, M.D., professor of psychiatry, Laura Bierut, M.D., assistant professor pf psychiatry, and others are studying the relationship between alcoholism and smoking in families. The information learned in this and other studies should allow better public health messages to be developed and might suggest additional drug interventions to help those who have started smoking.

Magnetic brain surgery
In 1998, Ralph G. Dacey Jr., M.D. performed the world's first magnetic stereotactic surgery to biopsy a human brain tumor using an indirect route to the tumor. The route is designed to avoid regions that would normally be entered when a surgeon manually inserts a surgical tool straight at a site. The investigational computerized system allows surgeons to carefully manipulate surgical tools inside the brain through the use of a catheter driven by precisely controlled magnetic fields. Dacey is the Edith R. and Henry G. Schwartz Professor and head of neurological surgery at the School of Medicine.

New cancer therapies
For many patients with advanced forms of cancer, experimental drugs and other cutting-edge therapies provide a glimmer of hope when existing methods fail. Paula M. Fracasso, M.D., Ph.D., designs and implements research studies that test the safety and effectiveness of brand-new therapies for cancer patients. These studies help to define maximum tolerated doses of new anticancer agents and enhance understanding of exactly how these therapies affect the disease. Together with Howard McLeod, Pharm.D., Fracasso is looking specifically at novel agents that block cancer cells from expanding, called cell cycle inhibitors, and growing, called signal transduction inhibitors. In addition, she is involved in the early clinical development of drugs, which given in combination with chemotherapy, may reverse resistance and improve survival in patients with cancer. Fracasso is associate professor of medicine and leader of the Siteman Cancer Center's Developmental Therapeutics Program. McLeod is associate professor of medicine, genetics, and of pharmacology and molecular biology, and also directs the Siteman Cancer Center's pharmacology core.

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