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| Vol. 21, No. 21 |
| November 15, 1999 |
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A Conversation With Dr. John Mendelsohn
Q Congratulations on receiving the Jill Rose Award recently. How did that come about? A The Breast Cancer Research Foundation in New York is raising money for leading investigators in the area of breast cancer. For many years, our breast cancer program here at M. D. Anderson has received support. The reason they gave this award for pioneering research in breast cancer to me is the release of Herceptin®, a new form of breast cancer therapy for general use, which is the culmination of a decade of pioneering research and clinical trials carried out in many locations. Herceptin® is a monoclonal antibody which binds to the surface of cells on a receptor for growth factors. This receptor is called HER2. Now, the original idea of producing a molecule that could block a growth factor receptor came from my laboratory in the early 1980s when I was directing the cancer center at the University of California-San Diego. We made an antibody against a close cousin of HER2 called the EGF receptor, which we hypothesized could block the receptor so that it could not be stimulated and could thereby block cell proliferation. We were able to show that this hypothesis was correct for cancer cells growing in culture and for human cancer cells growing in mice. Stimulated by work being done in Israel, we explored the idea that combining chemotherapy with an antibody that blocked a receptor could augment the efficacy of chemotherapy, specifically, the three best drugs in use for breast cancer, doxorubicin, paclitaxel and cisplatin. Subsequently, we asked similar questions in the area of radiotherapy, and it was shown experimentally that our antibody against the EGF receptor could synergize with radiotherapy. Clinical trials with our antibody, in combination with chemotherapy or radiotherapy, are seeing promising results. Meanwhile, the clinical trials with monoclonal antibody Herceptin® against HER2 have moved along quickly. They have demonstrated that patients with breast cancer, when treated with the combination of Herceptin® and either doxorubicin or paclitaxel have enhanced clinical responses. The FDA has approved this as a standard therapy. So this is a whole new way of treating cancer. It has been an unusual thrill because I've seen the work from the hypothesis through the laboratory and finally into good outcomes in the clinic. That work covered 14 years. Q It's an exciting time for cancer therapy. What do you see coming in the near future? A Well, we now know what causes cancer. It's caused by mutations or malfunction of a few hundred critical genes that control cell proliferation. We didn't know that a decade ago. Some of those genetic problems are hereditary, but most are acquired. The most common cause of these mutated genes is carcinogens from smoking. If everyone who smoked quit, one-third of all cancers would disappear. It does not cause just lung cancer, but cancer of the mouth, the upper respiratory tree, bladder, prostate, pancreas and possibly breast. I just can't say enough about that. Imagine, a third of all these resources we need to fight cancer wouldn't be necessary. So we have identified risks. And we are identifying risks at the molecular level, so we can give counseling to people who have inherited some of these genes. We also can diagnose cancer earlier by detecting genetic abnormalities in just a few cells, whereas x-rays won't pick up a tumor until there are 5 billion malignant cells. We're now developing new therapies that target those malfunctioning genes, as I discussed earlier. Five years ago, there were less than a dozen exciting drugs in cancer treatment. Now there are hundreds of exciting potential anti-cancer drugs coming from the major pharmaceutical companies. It's a wonderful challenge finding the ones that will work the best and getting those to the patient quickly. We're confident that many of them will work. Q Several academic health centers around the country are having a pretty hard time financially. How's M. D. Anderson doing? A Yes, some have had a hard time - especially those tied to medical schools. The major reason is, of course, the change in how payment is made for care. It's now through HMOs and managed care. Academic medical centers have sometimes not reacted well to this - for example, buying physician practices and finding that this is even a further drain. M. D. Anderson is in a fortunate position and there are several reasons we continue to have positive margins - which we put right back into the hospital, the physical plant and research. We get support from the state, a great majority of which we spend on indigent health care, about $100 million for indigent Texans with 30 percent of them in Harris County. So that is covered and we don't have to pull that money out of what is coming in from paying patients. Another reason that we may be doing better than some academic health centers is that we have a very diverse patient base: a quarter of our patients come from the Houston area, another quarter from the rest of the state of Texas and the remaining half of our patients from the rest of the U.S. and around the world. People who have cancer want to come to a place with outstanding clinical expertise - and outstanding research that's available if standard therapy doesn't achieve a cure. Yet another reason for our continued success is that we are one of just 10 federally designated free-standing cancer centers that are exempt from DRG [Medicare Diagnostic Related Groups] requirements; we are paid on a per diem basis rather than a lump sum basis because of the complexity of many of the cases we manage. Q Have there been some disappointments for you, some things that have not happened as fast as you'd hoped for? A Well, I think the good news is that we have learned a whole lot. When I was in training, I saw a lot of women with breast tumors the size of golf balls. Today we don't see that. If a woman feels something the size of a pea, she dashes to see her doctor for a mammogram. The bad news is that we haven't put into practice what we have learned as well as we might have. Lung cancer kills more women than breast cancer, but more young women are smoking than ever before. So that's very disappointing to us. You know, if everyone had a periodic exam of their bowel - a colonoscopy - we'd cut the rate of colon cancer by up to 50 percent. But that procedure is not covered by most insurance plans. Q You're a physician, researcher, teacher and an administrator. Which takes priority? A I don't do them all at once! From the very beginning, I was always interested in the chemical processes that controlled human life. When I was an undergraduate, I discovered I liked people as much as I did science, so I thought medicine would be perfect for me. But during my career at the University of California and at Memorial Sloan Kettering, I assumed more and more administrative positions directing programs and departments. So today I have no patients per se, none that I manage directly. I don't run my own research lab these days, though I collaborate on EGF receptor research with scientists and clinical investigators at M. D. Anderson and elsewhere. My challenge these days is managing the mission of this fabulous institution. That keeps me very busy. - ROGER WIDMEYER
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